NATIONAL INSTITUTES OF HEALTH 

REPORT OF THE AUTOIMMUNE DISEASES COORDINATING COMMITTEE 

October 2000 
FOREWORD

Autoimmune diseases result from a dysfunction of the immune system in which the body 

attacks its own organs, tissues and cells. Physicians and scientists have identified more than 70 

clinically distinct autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, 

immune-mediated diabetes, and systemic lupus erythematosus. While many autoimmune 

diseases are rare - affecting fewer than 200,000 individuals - collectively, these diseases afflict 

millions of Americans, an estimated five percent of the population. The social and financial 

burden of these chronic, debilitating diseases is immense, and includes poor quality of life, high 

health care costs, and substantial loss of productivity. 

The past two decades of intensive and highly productive research on the immune system 

have resulted in a wealth of new information and extraordinary growth in conceptual 

understanding. These accomplishments now provide promising opportunities for major 

advances in the diagnosis, treatment, and prevention of autoimmune diseases. The National 

Institutes of Health (NIH) stands at the forefront of many of these accomplishments. Because 

autoimmune diseases span many organ systems and clinical disciplines, multiple NIH institutes, 

offices, and centers support research in this area in collaboration with a wide range of 

professional and patient advocacy organizations. NIH has placed a high priority on coordination 

to ensure the effective participation of public and private organizations and the efficient use of 

research resources. 

To facilitate collaboration among those NIH components, other Federal agencies, and 

private organizations with an interest in autoimmune diseases, the NIH established the 

Autoimmune Diseases Coordinating Committee in 1998, under the direction of the National 

Institute of Allergy and Infectious Diseases. Since its inception, the Committee has analyzed a 

wide range of ongoing and planned research programs and has developed cross-cutting 

initiatives to address key aspects of autoimmunity. In addition, the Committee has established 

workgroups to foster scientific collaborations and to develop research initiatives in a variety of 

promising areas, including new therapeutic approaches such as the induction of immune 

tolerance, disease prevention, and the role of gender, genetics, infectious agents, and 

environmental factors in disease susceptibility, onset, and progression. 

In the 2lst century there will be unprecedented opportunities to understand autoimmune 

diseases at the molecular and genetic levels. A major goal of the Autoimmune Diseases 

Coordinating Committee is to forge a conceptual and mechanism-based understanding that 

emphasizes features shared among these disorders. This will enable scientists and clinicians to 

more rapidly translate new knowledge into more effective treatments. The following report 

highlights the importance of collaborative efforts in achieving these goals. 

Ruth Kirschstein, M.D. 

Principal Deputy Director 

National Institutes of Health 
TABLE OF CONTENTS 

Executive Summary............................................................................................................... i


I. Introduction................................................................................................................ 1


Scope of this Report................................................................................................... 1


The Impact of Autoimmune Diseases........................................................................ 1


Establishment of the Autoimmune Diseases Coordinating Committee..................... 2


II. The NIH Investment in Research on Autoimmune Diseases..................................... 3


Overview.................................................................................................................... 3


Planning and Implementation of FY1999 Congressional Appropriation for


Research in Autoimmunity .................................................................................. 4


Major Research Programs by Thematic Areas .......................................................... 5


Therapeutics................................................................................................... 6


Prevention ...................................................................................................... 7


Genetics.......................................................................................................... 8


Infectious Agents and Environmental Factors............................................... 9


Pathogenesis and Immune Dysfunction......................................................... 9


Epidemiology and Risk Factors..................................................................... 10


Organ Specificity ........................................................................................... 10


Animal Models............................................................................................... 10


Nursing, Behavioral, and Health Services Research ..................................... 11


Research Resources ....................................................................................... 12


Scientific Symposia, Workshops, and Publications................................................... 13


III. Opportunities.............................................................................................................. 14


Immune Tolerance ..................................................................................................... 15


Improved Diagnosis and Patient Management .......................................................... 15


Genetics...................................................................................................................... 16


Gender and Autoimmunity ...................... ................................................................. 16


Vaccines for Autoimmune Diseases .......................................................................... 17


Infectious Agents and Environmental Factors........................................................... 17


IV. Conclusions................................................................................................................ 17


Appendix A: Autoimmune Diseases Coordinating Committee Roster .................... 18


Appendix B: Autoimmune Diseases Coordinating Committee Mission Statements 20


Appendix C: FY 1999 Autoimmunity Research Initiatives...................................... 23


Appendix D: NIH-Sponsored Initiatives in Autoimmune Diseases Research


FY 1996 to FY 2001 .......................................................................... 24


Appendix E: List of Abbreviations and Acronyms................................................... 26
EXECUTIVE SUMMARY 

The National Institutes of Health (NIH) supports a wide range of research projects and programs 

in autoimmune diseases. Autoimmune diseases result from a disordered attack of the immune 

system on the body’s own tissues, and they disproportionately affect women. These chronic and 

disabling diseases include insulin dependent diabetes mellitus (type 1 diabetes), multiple 

sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis, inflammatory bowel 

disease, psoriasis, uveitis, and autoimmune thyroid disease. 

This document, Report of the NIH Autoimmune Diseases Coordinating Committee, summarizes 

recent basic and clinical research programs supported by the NIH and non-Federal organizations, 

highlighting coordination and collaborative activities in 10 thematic areas, recent and ongoing 

activities of the Autoimmune Diseases Coordinating Committee, and emerging opportunities to 

improve treatment and develop preventive approaches for autoimmune diseases. Twenty-two 

NIH Institutes, Centers, and Offices; the U.S. Food and Drug Administration; the Centers for 

Disease Control and Prevention; the U.S. Department of Veterans Affairs; and 10 private 

organizations with an interest in autoimmune diseases are represented on the Committee. The 

research programs supported by these groups comprise a broad range of basic, pre-clinical, and 

clinical endeavors addressing many different diseases, organ systems, and aspects of 

autoimmune disease. This report is organized in four major sections: 

1.	 Introduction, outlining the medical impact of autoimmune diseases, the establishment and 

activities of the Autoimmune Diseases Coordinating Committee, and collaborative planning 

and implementation of the FY 1999 Congressional Appropriation for Research in 

Autoimmunity; 

2. NIH programs and activities in autoimmune diseases organized by thematic area; 

3.	 Opportunities, emphasizing emerging areas of science that offer exciting possibilities for 

improving the lives of patients and others at risk for development of autoimmune diseases; 

and 

4. Conclusions. 

I. INTRODUCTION 

Impact of Autoimmune Diseases. Autoimmune diseases include more than 70 different 

disorders affecting approximately 5 percent of the U.S. population. Women are 

disproportionately affected by most diseases, and minorities are at increased risk for certain 

diseases; for example, African Americans are at higher risk for development of SLE. The 

chronic nature of these diseases leads to increased health care costs, including hospitalizations 

and physician visits. 

Establishment of the Autoimmune Diseases Coordinating Committee. Both House and 

Senate Appropriations Committee reports in 1998 encouraged the establishment of an NIH 

Autoimmune Diseases Coordinating Committee. The NIH established the committee under the 

direction of the National Institute of Allergy and Infectious Diseases (NIAID) in June 1998. In 

addition to NIH Institutes, Centers, and Offices, other Federal agencies with an interest in 

i 
autoimmune diseases were invited to participate, along with private organizations that support 

research in this area. This allows maximum coordination among groups working in areas of 

complementary and shared interests. The Committee has collected information on current 

research activities and funding levels, collaborated in developing and implementing scientific 

initiatives that address the intent of the FY 1999 Congressional Appropriation for Research in 

Autoimmunity, and recently established working groups to prospectively develop collaborative 

research programs. 

Planning and Implementation of FY 1999 Congressional Appropriation for Research in 

Autoimmunity. In FY 1999, Congress included $30 million in the appropriation of NIAID for 

support of autoimmunity research. NIH staff developed seven new trans-NIH initiatives and 

approved an additional nine planned or ongoing programs to receive additional funding. 

II. THE NIH INVESTMENT IN RESEARCH ON AUTOIMMUNE DISEASES 

Overview. The majority of NIH support in autoimmune disease research is through unsolicited 

investigator-initiated research grants awarded by the Institutes, Centers, and Offices. The 

Autoimmune Diseases Coordinating Committee has enhanced trans-NIH exchange of 

information in these areas; facilitated coordination of solicited research among NIH Institutes, 

Centers, and Offices and private organizations; and promoted prospective planning and 

collaboration in new areas of research. 

Major Research Programs by Thematic Areas. The Committee has collected data from its 

members concerning their support of autoimmunity research. This report summarizes the goals 

and achievements of funded NIH research programs organized in thematic areas. 

• Programs in therapeutics include the Immune Tolerance Network, which will support 

clinical trials of promising new tolerance induction agents and development of novel assays 

or biomarkers of the tolerant state; Clinical Trials of Stem Cell Transplantation for Treatment 

of Autoimmune Diseases, which will perform safety and efficacy trials of this emerging but 

expensive approach; Autoimmunity Centers of Excellence, a network of basic and clinical 

research Centers focused on multiple autoimmune diseases, which will encourage interaction 

of basic scientists with clinical specialists, e.g., gastroenterologists, neurologists, and 

endocrinologists; Pilot Trials on Innovative Therapies for Rheumatic and Skin Diseases, 

which will support six clinical trials in rheumatic and skin diseases; and Human Islet 

Transplantation into Humans, which will perform clinical studies using new methods to 

induce immune tolerance to prevent recurrence of the autoimmune destruction of the beta 

cells in the islet and prevent transplant rejection. 

• Research in prevention includes the nationwide Diabetes Prevention Trial—Type 1 and new 

Basic Immunology Vaccine Research Center, which will support fundamental research 

relevant to the design and development of improved vaccines for immunologic and infectious 

diseases. 

• Genetics research includes the Multiple Autoimmune Diseases Genetics Consortium to 

collect clinical data and samples from families in which two or more individuals are affected 

ii 
by two or more autoimmune diseases; the North American Rheumatoid Arthritis Consortium, 

a collaborative group dedicated to the collection and distribution of DNA and clinical 

information from families with rheumatoid arthritis; the International Histocompatibility 

Working Group, which develops, standardizes, and distributes highly sensitive reagents for 

tissue typing for disease risk assessment and transplantation matching; the National 

Ankylosing Spondylitis Consortium, a collaborative group dedicated to the collection, 

distribution, and analysis of DNA and genetic information from families with ankylosing 

spondylitis; and the Genetics of Juvenile Rheumatoid Arthritis (JRA) Study to collect and 

analyze clinical and genetic data on children with JRA. 

• The role of infectious agents and environmental factors in the induction of autoimmune 

diseases was addressed in a recent solicitation of innovative research projects involving 

environmental toxins, infectious agents, and their interaction with genetic background in 

autoimmune diseases. 

• Research into the pathogenesis and immune dysfunction in autoimmune diseases represents 

the largest area of research because studies in basic immunology, self-tolerance, mucosal 

immunity, and adaptive/innate immunity are the foundation of new approaches to treatment. 

• Studies in epidemiology and risk factors are particularly important because autoimmune 

diseases disproportionately affect women and certain minority/ethnic groups. DAISY 

(Diabetes Autoimmunity Study in the Young) is a unique approach to this area in type 1 

diabetes. Other natural history studies could facilitate discovery of immune surrogate 

markers, which are a critical need for clinical trials. 

• Studies in organ specificity explore why the pancreas is targeted in type 1 diabetes, the joint 

in rheumatoid arthritis, and the central nervous system in multiple sclerosis. The NIH 

supported innovative approaches to this important question under a recent research 

solicitation. 

• Development of improved animal models will enhance studies in all areas of autoimmunity 

research. In particular, models that more accurately reflect human autoimmune diseases are 

needed. The NIH Rat Autoimmune Model Repository and Development Center will 

facilitate the development and availability of genetically characterized, disease-free 

laboratory rats for autoimmune disease research. 

• Quality of life is severely compromised for many patients with chronic diseases. Studies 

supported under nursing, behavioral, and health services research include new approaches 

to pain and disability management, training of professionals to help patients live with their 

disease, and the effect of stress, mood, and pain on the clinical manifestations and 

progression of disease. 

• Research resources include development of new technologies in both basic and clinical 

research and establishment of clinical registries, animal repositories, and databases to support 

research in the nine other thematic areas. 

iii 
Scientific Symposia, Workshops, and Publications. Support for scientific workshops in 

emerging areas of research, e.g., infectious etiologies of chronic diseases, discovery of human 

immune response genes, linking environmental agents and autoimmune diseases, 

neuropsychiatric manifestations of systemic lupus erythematosus, and accelerated atherosclerosis 

in systemic lupus erythematosus, is crucial in bringing new investigators and fresh approaches to 

important areas. A unique meeting called new Immunotherapies for Autoimmune Diseases 

included lay and scientific sessions. This format encouraged informal exchange and increased 

understanding between laypersons and scientists. 

III. OPPORTUNITIES 

In the 21st century, there will be unprecedented opportunities to understand autoimmune 

diseases at the molecular and genetic levels. A major goal of NIH research in this area is to 

forge a conceptual and mechanism-based understanding that emphasizes features shared among 

these disorders and facilitates discovery of new approaches that can be applied to autoimmune 

diseases affecting different organ systems. This will enable scientists and clinicians to more 

rapidly translate new knowledge into more effective treatments for a wide range of autoimmune 

diseases. Specific areas of particular opportunity include the following: 

• Immune Tolerance—Several novel biologics are in early clinical testing in patients with 

autoimmune diseases. 

• Improved Diagnosis and Patient Management—New technologies will allow improved 

diagnosis, staging, and risk assessment. 

• Genetics—Emerging information technologies will allow incorporation of new data from the 

Human Genome Project to increase understanding of the genetic component of autoimmune 

diseases. 

• Gender and Autoimmunity—Why women are affected disproportionately by these diseases 

is not known; new insights into differences in immune responses of men and women are 

emerging. 

• Vaccines for Autoimmune Diseases—Although no vaccine for any autoimmune disease 

exists at the present time, feasibility is clear from animal studies. Vaccines for autoimmune 

diseases will be distinct from vaccines given to prevent infectious diseases; vaccines for 

autoimmune diseases will turn off a destructive immune response directed at the body’s own 

tissues. Vaccine development is a long and collaborative process involving many Federal 

agencies in partnership with academia and industry. The Institute of Medicine recently 

placed a high priority on development of vaccines for autoimmune diseases. 

• Infectious Agents and Environmental Factors—Infectious agents and environmental factors 

are postulated to play a role in the etiology of autoimmune diseases. Recently, several 

possible mechanisms in animal models have been identified. Further clarification of the role 

of these agents in the pathogenesis of disease is needed. 

iv 
IV. CONCLUSIONS 

The U.S. investment in biomedical research has yielded major advances in health and quality of 

life for Americans. However, with each advance comes a new set of challenges. The major 

challenges facing research in autoimmune diseases today are (1) development of a mechanismbased, conceptual understanding of autoimmune disease; (2) translation of this knowledge into 

new, broadly applicable strategies for treatment and prevention of multiple diseases; and (3) 

development of sensitive tools for early and definitive diagnosis, disease staging, and 

identification of at-risk individuals. Through a wealth of collaborative programs outlined in this 

report, NIH-supported scientists are vigorously pursuing these goals. 

v 
I. INTRODUCTION 

Scientific advances over the past several decades have revolutionized our understanding of the 

human immune system and have contributed substantially to improvements in the treatment of 

many immune-mediated diseases. The NIH has been at the forefront of many of these advances, 

including the awareness that a number of chronic diseases of previously unknown origin, 

including autoimmune disorders, arise from dysregulation of immune responses. As we enter the 

21st century, these advances provide a solid foundation for translating basic research into 

clinical applications. Because autoimmune diseases affect multiple organ systems, many NIH 

Institutes, Centers, and Offices support research in this area. Therefore, NIH has placed a high 

priority on trans-Institute coordination to ensure the most effective use of research resources. 

SCOPE OF THIS REPORT 

This report focuses on (1) recent basic and clinical research programs on autoimmune diseases 

supported by the NIH and non-Federal organizations; (2) NIH activities to coordinate scientific 

planning and sponsorship of research programs, including collaborative efforts that address 

recent congressional interest in this area; and (3) future scientific opportunities and plans for 

trans-NIH initiatives and public-private research partnerships. 

THE IMPACT OF AUTOIMMUNE DISEASES 

Autoimmune diseases are a group of more than 70 chronic disorders resulting from dysregulation 

of immune responses, leading the body to attack its own cells and tissues. Organ-specific 

autoimmune diseases are characterized by immune-mediated injury localized to a single organ or 

tissue, e.g., the pancreas in type 1 diabetes and the central nervous system in multiple sclerosis 

(MS). In contrast, non-organ-specific diseases, such as systemic lupus erythematosus (SLE), are 

characterized by immune reactions against many different organs and tissues, resulting in 

widespread injury. 

Collectively, autoimmune diseases affect at least 5 percent of the U.S. population. Statistics on 

the medical impact of selected autoimmune diseases include the following: 

• Rheumatoid Arthritis (RA): 2.1 million cases in the United States, including 30,000 to 

50,000 children; 80 percent with limitations in function; afflicts twice as many women as 

men; on an annual basis, results in 25,000 hospitalizations, 2.1 million lost workdays, and 12 

physician visits per patient. 

• Type 1 diabetes: 300,000 to 500,000 cases in the United States, including 123,000 younger 

than 20 years of age. 

• Multiple Sclerosis (MS): 250,000 to 350,000 cases in the United States, resulting in 25,000 

hospitalizations per year. 

• Systemic Lupus Erythematosus (SLE): Approximately 240,000 cases in the United States; 

disproportionately affects women and minorities. 

1 
• Inflammatory Bowel Disease (IBD): More than 800,000 cases in the United States; more 

than two-thirds due to ulcerative colitis and approximately one-third due to Crohn’s disease; 

2.3 million outpatient visits per year and more than 31,000 restricted-activity days annually. 

• Autoimmune Thyroid Disease (ATD): The mean incidence of Hashimoto’s disease is 3.5 

cases per 1,000 women per year (0.8 cases per 1,000 men); the prevalence of Graves’ disease 

in England is 10 times higher in women than men, or 27 per 1,000 women. 

ESTABLISHMENT OF THE AUTOIMMUNE DISEASES COORDINATING 

COMMITTEE 

In FY 1998, the reports of both the Senate and the House Appropriations Committee addressed 

the importance of coordination of NIH-supported research activities relating to autoimmune 

diseases. 

House Report Language—“Autoimmunity is at the root of a family of over 80 

interrelated major diseases affecting some 50 million Americans. The Committee 

suggests that the Director convene some type of coordinating body for autoimmune 

disease research at NIH, comprised of the various Institutes supporting research in 

this area, for the purpose of synergizing research among the Institutes on 

autoimmune related disorders. The resulting coordinated and improved use of 

existing research funds will facilitate and accelerate the application of important 

findings among the many research programs dealing with autoimmune diseases.” 

Senate Report Language—“Autoimmunity is the root of a family of over 80 

interrelated diseases that cut across the Institutes at the NIH. The Committee is 

aware of a recommendation to establish a coordinating council on autoimmune 

disease research to improve the use of existing research funds and facilitate the 

application of important findings among the many research programs dealing with 

autoimmune diseases at the NIH. The Committee requests that the Director give 

careful consideration to the creation of such a committee.” 

The NIH established the Autoimmune Diseases Coordinating Committee (ADCC) in 1998 under


the direction of the National Institute of Allergy and Infectious Diseases (NIAID). Committee


members include 22 NIH Institutes, Offices, and Centers that support research on autoimmune


diseases; the U.S. Food and Drug Administration (FDA); the U.S. Department of Veterans


Affairs (VA); the Centers for Disease Control and Prevention (CDC); and private organizations


that sponsor research in this area (Appendixes A and B). Since its initial meeting in June 1998
,


the Committee has (1) collected and analyzed information on current research activities an
d


funding levels and (2) established multi-Institute collaborative working groups in areas o
f


common interest and relevance to multiple autoimmune diseases. In addition, the Committee’
s


efforts have facilitated a variety of other activities to further enhance coordination of research


and increase partnerships between public and private organizations. Examples include the


following:


2 
• Extensive collaboration among many NIH Institutes, Centers, and Offices in planning and 

cosponsoring new research initiatives resulting from the additional FY 1999 congressional 

appropriation for autoimmunity research (as detailed below). 

• Facilitation of new and continuation of established public-private research partnerships, e.g., 

linking the NIH with the Juvenile Diabetes Foundation International (JDFI), the Arthritis 

Foundation, the National Multiple Sclerosis Society, and the Crohn’s and Colitis Foundation 

of America (CCFA). 

• Cosponsorship of workshops and scientific symposia, e.g., linking the NIH and JDFl, 

Arthritis Foundation, American College of Rheumatology, and American Autoimmune 

Related Diseases Association (AARDA). 

• Participation of NIH staff in scientific planning activities of non-Federal organizations, e.g., 

the National Multiple Sclerosis Society, Alliance for Lupus Research, and JDFI. 

II. THE NIH INVESTMENT IN RESEARCH ON AUTOIMMUNE DISEASES 

OVERVIEW 

Major mechanisms of NIH support include individual research project grants, program project 

grants, contracts, and cooperative agreements. Investigator-initiated, unsolicited research 

projects make up the largest share of the NIH investment in this area. The Autoimmune 

Diseases Coordinating Committee serves as an important forum for trans-Institute exchange of 

information pertaining to the unsolicited research portfolios of individual Institutes, Centers, and 

Offices. The activities of the Autoimmune Diseases Coordinating Committee also include interInstitute collaboration and coordination in the development, review, award, and postaward 

monitoring of solicited research programs. To enhance trans-NIH scientific planning, the 

Autoimmune Diseases Coordinating Committee has categorized autoimmune disease-related 

research activities in 10 thematic areas highlighted below. 

In FY 1999, NIH Institutes committed more than $393 million in support of basic, preclinical, 

and clinical research on autoimmune diseases (Figure 1). 

3 
NCCAM ($1) 

NIDCR ($5) 0%

NIDCD ($2) 

1% 

NCRR ($14) 

4% 

NIEHS ($2) 

1% 

NIDDK ($74) 

19% 

NINR ($2) 

1% 

NHGRI ($1) 

0% 

NINDS ($51) NIA ($1) 

0% 

NICHD ($6) 

NIMH ($7) 2%

2% 

NIAMS ($69) 

NCI ($4) 

NIAID ($78) 

20% 

1% 

1% 

NHLBI ($26) 

7% 

NEI ($49) 

13% 

18% 

13% 

Figure 1. Total NIH Funding for Autoimmune Diseases in FY 1999 by Institute ($ in Millions) 

PLANNING AND IMPLEMENTATION OF FY 1999 CONGRESSIONAL 

APPROPRIATION FOR RESEARCH IN AUTOIMMUNITY 

The Conference Report accompanying H.R. 4329, the Omnibus Consolidated and Emergency 

Supplemental Appropriation for FY 1999, contained the following language: 

“The conference agreement includes $1,570,102,000 for the NIAID instead of 

$1,540,102,000 as proposed by the Senate and $1,470,460,000 as proposed by the House. 

Autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, diabetes, and lupus 

affect millions of Americans and disproportionately affect women and minorities. It is 

believed that enhanced research in this area holds the potential to cure and prevent many 

diseases. In addition, more needs to be known about the specific environmental agents 

that are causing the onset of the diseases, genetic susceptibility, and how the body 

regulates the autoimmune response. Therefore, NIAID is strongly urged to expand its 

research efforts to capitalize on recent discoveries of autoimmune reactions and newly 

developed treatments that can suppress immune responses without toxic side effects. It is 

understood that the NIH Autoimmune Diseases Coordinating Committee should provide 

greater coordination and renewed focus for autoimmunity research on the NIH campus.” 

The prior establishment of the trans-NIH Autoimmune Diseases Coordinating Committee 

facilitated a coordinated scientific planning process to design and implement new research 

programs in response to congressional intent. The guiding principles of this planning process 

included an emphasis on (1) cross-disciplinary research addressing multiple autoimmune 

diseases; (2) support for a mechanism-based approach, encompassing fundamental investigations 

of disease pathogenesis and clinical trials involving new diagnostic and therapeutic approaches; 

and (3) selected research programs focusing on specific diseases and/or extraordinary scientific 

opportunities. 

Seven new trans-NIH initiatives emerged from this process, and nine previously planned or 

ongoing initiatives received increased support (Appendix C). The majority of the new and 

previously planned initiatives involved joint sponsorship by multiple NIH components. Figure 2 

shows the distribution of dollars among the NIH Institutes and Centers and major project areas. 

4 
5

eas

• 

• 

18.3M

Dollar Distribution

N IA M S $ 3 .9 M

N ID D K $ 3 .1 M

N C R R $ 0 .9 M

N H L B I $ 1 .1 M

N E I $ 1 .8 M

N IE H S $ 0 .6 M

N IN D S $ 0 .3 M

NIAID

$

Project Ar

Immune Tolerance

• Stem Cell Transplantation

• Organ Damage

• New Imaging Technologies

• Environment/Infection/Gene Interaction

• Autoimmunity Centers of Excellence

• Primate Transplantation Models

• Rheumatic and Skin Diseases

• Genetics

• Immunologic Clinical Trials/Clinical Markers

Immunological Mouse Mutants Phenotyping

• Human Immunology Centers of Excellence

Figure 2. Distribution of FY 1999 Autoimmunity Funds: NIH Institutes and Centers and Major Project Areas

MAJOR RESEARCH PROGRAMS BY THEMATIC AREAS

The development of autoimmune diseases reflects complex interactions between the immune

system, genetic background, and environmental factors. refore, NIH-supported research is

broad in scope, ranging from understanding the determinants of disease to developing effective

therapies and strategies for preventing disease. members of the NIH Autoimmune Diseases

Coordinating Committee code the research that they support according to thematic areas. e

latest figures available are for FY 1998 (Figure 3). IH Institutes,

Centers, and Offices and non-Federal partners coordinate efforts through research partnerships,

sponsorship of workshops, and establishment of databases and other research resources

accessible to the research community (Appendix D).

Figure 3. 998 NIH Autoimmune Diseases Funding by Thematic Area

Epidemiology 

and Risk Factors

5%

Genetics

8%

Prevention

2%

Organ Specificity

10%

Infectious Agents 

and 

Environmental 

Factors 5%

Pathogenesis 

and

Immune 

Dysfunction 53%

Therapeutics

11%

Animal Models

3%

Nursing, 

Behaviorial, and 

Health Services 

Research

1%

Research

Resources

2%

The

The

Th

Within this framework, N

FY 1
THERAPEUTICS—The NIH investment in basic research has yielded the knowledge 

necessary to develop new therapeutic strategies for the treatment of immune-mediated diseases. 

These preclinical research advances have provided an impetus for established pharmaceutical 

and emerging biotechnology companies to develop novel agents that may more selectively 

inhibit the deleterious immune responses in autoimmune diseases. The NIH is capitalizing on 

these advances through increased sponsorship of clinical trials, often in partnership with 

industry. Major ongoing and new clinical research programs include the following: 

• Immune Tolerance Network. The successful induction of immune tolerance is a major 

therapeutic goal for the treatment of many immune-mediated diseases. Tolerogenic 

approaches seek to modulate or block deleterious immune responses critical in the 

development and progression of disease and in the rejection of transplanted organs, tissues, 

and cells. In 1998, NIAID published a long-term research plan to accelerate the study of 

immune tolerance, particularly in the clinical setting 

(http://www.niaid.nih.gov/publications/immune/contents.htm). A major new clinical 

research program emanating from this research plan was established in September 1999, 

under the joint sponsorship of NIAID, the National Institute of Diabetes and Digestive and 

Kidney Diseases (NIDDK), and the JDFI. This unique consortium of more than 40 

institutions in the United States, Canada, Western Europe, and Australia is dedicated to the 

clinical evaluation of promising tolerance induction therapies in four areas: kidney 

transplantation, islet transplantation for type 1 diabetes, autoimmune disorders, and asthma 

and allergic diseases (http://www.immunetolerance.org). The network will also develop 

assays and biomarkers to measure the induction, maintenance, and loss of immune tolerance 

in humans. Various clinical studies are in development for many autoimmune diseases, 

including MS, RA, type 1 diabetes, and SLE. 

• Stem Cell Transplantation for the Treatment of Autoimmune Diseases. Stem cell 

transplantation is currently under evaluation for treatment of multiple autoimmune diseases. 

Several studies of safety have been completed; however, case-controlled studies of efficacy 

have not yet been conducted. In FY 1999, NIH initiated a coordinated research effort to 

study the safety and effectiveness of these treatment regimens for several autoimmune 

disorders. 

• Pilot Clinical Trials on Innovative Therapies for Rheumatic and Skin Diseases. This 

research initiative was implemented in FY 1999, under the leadership of the National 

Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), with several NIH 

Institutes, to develop innovative therapies for the treatment of rheumatic and skin diseases. 

Awards were made for research on the following diseases: Wegener’s granulomatosis, RA, 

scleroderma, SLE, and ankylosing spondylitis (AS). 

• Autoimmunity Centers of Excellence. Four research centers were established in FY 1999 

to support collaborative basic and clinical research on autoimmune diseases, including 

single-site or multisite clinical trials of immunomodulatory therapies. The Centers bring 

together many different subspecialists (e.g., neurologists, gastroenterologists, and 

rheumatologists), as well as basic scientists, increasing clinical and research collaborations in 

autoimmunity. 

6 
• Clinical Trials and Clinical Markers in Immunologic Diseases. In FY 2000, NIAID with 

several NIH components will begin a new research program focused on orphan clinical trials 

of immunomodulatory treatments for immune-mediated diseases, including autoimmune 

disorders, and the development of biological markers to measure disease activity, risk, and 

therapeutic effect. 

• Hyperaccelerated Awards for Mechanistic Studies of Immune Disease Trials. This 

existing research program supports mechanistic studies in conjunction with clinical trials of 

immunomodulatory interventions for immune-mediated diseases. Multiple NIH Institutes, 

Centers, and Offices are cosponsoring this program, which incorporates expedited procedures 

for review and award of meritorious grant applications within 13 weeks of submission. 

• Cyclophosphamide in Scleroderma Pulmonary Disease. In FY 1999, the National Heart, 

Lung, and Blood Institute (NHLBI) began an investigator-initiated clinical trial of 

cyclophosphamide in the treatment of the pulmonary fibrosis associated with systemic 

sclerosis. In systemic sclerosis, interstitial pulmonary fibrosis is frequent (80 percent) and is 

now the leading cause of death. The mortality rate of patients with impaired pulmonary 

function is 40 to 45 percent within 10 years of onset. Uncontrolled studies suggest that 

cyclophosphamide may stabilize or improve lung function in systemic sclerosis patients. The 

study is a 5-year, 13-center, parallel-group, double-blind, randomized, controlled, phase III 

clinical trial of oral cyclophosphamide versus placebo to assess the efficacy of 

cyclophosphamide in stabilizing or improving the course of pulmonary disease in 

scleroderma. NIAMS also contributes to the support of this study. 

• Human Islet Transplantation Into Humans. This program will support clinical studies 

using new methods to induce immune tolerance to prevent recurrence of the autoimmune 

destruction of beta cells in the islet and to prevent transplant rejection. The NIDDK, NIAID, 

and JDFI support this program. 

• New Strategies for the Treatment of Type 1 Diabetes. In FY 2000, the NIDDK, NIAID, 

and National Institute of Child Health and Development (NICHD) will begin a new program 

supporting clinical studies to test new approaches to treat type 1 diabetes, including studies 

of immunomodulation. 

PREVENTION—Knowledge of the genetic and environmental determinants of disease, coupled 

with a better understanding of human immunology, will provide the basis for the development of 

preventive approaches. Prevention or delay of disease onset for certain autoimmune diseases has 

been demonstrated in animal models. 

• Diabetes Prevention Trial—Type 1. Under the sponsorship of the NIDDK, NIAID, 

NICHD, CDC, JDFI, and the American Diabetes Association (ADA), this national multisite 

cooperative clinical trial is evaluating the use of parenteral and oral insulin for prevention of 

type 1 diabetes in high-risk and intermediate-risk relatives of patients with type 1 diabetes. 

The first results from this study are expected in FY 2002. 

• Basic Immunology Vaccine Research Centers. In FY 2000, NIAID will establish a new 

research program to support fundamental research relevant to the design and development of 

7 
improved vaccines for immunologic and infectious diseases. This effort will enable the 

application of basic immunologic principles to the rational design of prevention strategies. 

GENETICS—Certain autoimmune diseases have been linked to a particular set of genes called 

the major histocompatibility complex (MHC), known to be important in controlling immune 

responses. Recent findings suggest that other families of genes that regulate immune responses 

may be involved in the pathogenesis of autoimmune diseases. 

• North American Rheumatoid Arthritis Consortium. In FY 1997, the North American 

Rheumatoid Arthritis Consortium was established as part of a collaborative effort among 

NIAID, NIAMS, and the Arthritis Foundation (AF). Through this consortium, a registry and 

repository of clinical and genetic data has been developed as a research resource for the 

discovery of RA susceptibility genes. 

• Multiple Autoimmune Diseases Genetics Consortium. Under this FY 1999 research 

initiative, a repository of genetic and clinical data and samples is being developed from 

families in which two or more individuals are affected by two or more autoimmune diseases. 

This resource will promote research to advance the discovery of human immune response 

genes involved in autoimmunity. 

• Functional Genomics of the Developing Pancreas. This NIDDK research initiative will 

support the production, sequencing, and distribution of cDNA libraries for discovery and 

functional studies of genes regulating development of the normal and diabetic pancreas. 

• International Histocompatibility Working Group (IHWG). The National Cancer Institute 

(NCI), NHLBI, NIDDK, and NIAID support the IHWG to develop, standardize, and 

distribute highly sensitive reagents for tissue typing worldwide. These efforts enhance 

identification of healthy individuals at risk for development of autoimmune disorders and 

ensure that transplant recipients will receive optimally matched donor organs and tissues. 

• North American Spondylitis Consortium. NIAMS established this consortium in FY 1999 

to identify susceptibility genes for AS, a rare but painful disease of the spine primarily 

affecting men. Ten research centers and the Spondylitis Association of America are 

participating in this activity. 

• Juvenile Rheumatoid Arthritis Study. NIAMS expanded this registry in FY 1999 to 

collect DNA and to identify susceptibility genes for juvenile rheumatoid arthritis. 

• Lupus Registries and Repository. NIAMS established a registry and repository to collect 

clinical data and samples from patients with SLE and their families. This resource should 

assist investigators in identifying genes that determine susceptibility to lupus. A separate 

Registry for Neonatal Lupus will enhance the search for basic defects in neonatal lupus and 

may lead to improved diagnosis, treatment, and prevention methods. This registry is also 

supported by NIAMS. 

• Vitiligo Genetic Linkage Project. Vitiligo is an autoimmune disease resulting in patchy 

depigmentation of the skin, which is particularly disfiguring in dark-skinned individuals. The 

8 
aggregation of the disease in families is being utilized by Dr. Richard Spritz at the University 

of Colorado to map the vitiligo gene(s) in a U.S. and a United Kingdom cohort of vitiligo 

families. This project is supported by NIAMS. 

INFECTIOUS AGENTS AND ENVIRONMENTAL FACTORS—A growing body of 

research concerns the role of infectious agents in triggering certain chronic diseases, including 

autoimmune disorders. Recently, several mechanisms have been proposed for this association 

and have proven to be operative in animal models. 

• Environmental/Infectious/Genetic Interactions in Autoimmune Disease. In FY 1999, 

under the leadership of the National Institute of Environmental Health Sciences (NIEHS) 

with multiple collaborating NIH Institutes, Centers, and Offices, a research program was 

established to support innovative studies to elucidate the role of environmental and infectious 

agents in autoimmune diseases and to clarify their interaction with genes in modulating 

immune responses. Enhanced knowledge in this area will contribute to the discovery of new 

therapeutic and preventive strategies. 

• Carolina Lupus Study. The NIEHS Division of Intramural Research supports the Carolina 

Lupus Study to identify the role of infectious agents and environmental exposures in the 

development of lupus, with a particular focus on African American women, who are 

disproportionately affected by this disease. 

PATHOGENESIS AND IMMUNE DYSFUNCTION—Research in this area focuses on 

understanding the disease process, particularly the defects in the immune response that cause the 

body to attack its own tissues and cells. 

• Diabetes Centers of Excellence. This continuation of a longstanding basic research 

program is supported jointly by the NIDDK, NIAID, and JDFI and focuses on increasing 

understanding of the fundamental disease processes and mechanisms involved in diabetes. A 

majority of the projects supported under this program address type 1 diabetes. 

• NIAID-JDFI Interdisciplinary Programs in Autoimmunity. Five multidisciplinary 

projects are supported under this program to investigate the molecular, immunologic, and 

genetic mechanisms in the pathogenesis of autoimmunity. 

• Human Immunology Centers of Excellence. In FY 1999, NIAID established four new 

research centers focused on multidisciplinary approaches to define the mechanisms 

responsible for normal and pathologic human immune responses. 

• Innovative Research on Human Mucosal Immunity. The CCFA joined NIAID and the 

National Institute of Dental and Craniofacial Research (NIDCR) in sponsoring this FY 2000 

research initiative to promote innovative investigations of the human mucosal immune 

system and its role in the pathogenesis of autoimmune diseases, including IBD. 

• Innovative Research on Immune Tolerance. NIAID and NIDDK will cosponsor this 

initiative to support innovative research on mechanisms underlying long-term immune 

9 
tolerance and to identify novel targets for future drug development. These projects will 

begin in FY 2001. 

• Diabetes and Endrocrinology Research Centers and Diabetes Research Training 

Centers. A portion of these Centers supports basic and clinical research on type 1 diabetes 

and other autoimmune diseases. 

• Veterans Administration (VA) Medical Centers. Basic and clinical research on 

autoimmune diseases is supported by the VA Medical Research Service through merit review 

grants. A distinctive feature of VA-sponsored research is the high proportion of medical 

doctorate investigators supported at VA Medical Centers across the United States. 

EPIDEMIOLOGY AND RISK FACTORS—The incidence and prevalence of some 

autoimmune diseases appear to be increased in certain ethnic groups; for example, SLE, RA, and 

MS are increased in African American, certain Native American, and Caucasian populations, 

respectively. For many autoimmune diseases, relatively little is known about natural history 

preceding the onset of overt disease or about the genetic, behavioral, and environmental factors 

that contribute to disease progression. An expanded knowledge base in these areas would 

facilitate the design, implementation, and evaluation of prevention efforts. 

• DAISY (Diabetes Autoimmunity Study in the Young). This long-term study, supported 

by NIDDK and NIAID, includes collection and followup of two cohorts: (1) healthy siblings 

and offspring of people with type 1 diabetes and (2) healthy newborns with type 1 diabetesassociated MHC genes but without a family history of diabetes. The study is collecting and 

analyzing data on infections, vaccination, diet, MHC genes, and autoantibodies to beta cell 

antigens in these cohorts. 

ORGAN SPECIFICITY—Research in this area seeks to explain why the immune attack is 

limited to a specific organ in some autoimmune diseases (e.g., the central nervous system in 

MS), whereas in others, the tissue injury is widespread (e.g., SLE). Recent findings suggest that 

the target organ may play a more active role than previously thought in molding the tissuespecific immune responses. 

• Target Organ Damage in Autoimmune Diseases. Under the leadership of NIAMS, 

multiple NIH components, including NIAID, NIDCR, NIDDK, NHLBI, National Eye 

Institute (NEI), National Institute of Neurological Disorders and Stroke (NINDS), National 

Institute on Deafness and Communication Disorders (NIDCD), National Institute of Mental 

Health (NIMH), and Office of Research on Women’s Health (ORWH), developed a FY 1999 

research initiative to stimulate innovative and multidisciplinary studies of the involvement of 

target organs in autoimmune diseases. Knowledge gained in this area will make it possible to 

construct a more comprehensive picture of disease pathogenesis and will provide a scientific 

basis for new therapeutic interventions. 

ANIMAL MODELS—The development of improved animal models will enhance studies in all 

of the above areas. In particular, models that more faithfully mimic human disease are essential 

in the preclinical evaluation of new therapeutic approaches and the application of such 

approaches in the clinical setting. 

10 
• Nonhuman Primate Transplant Tolerance Cooperative Study Group. In FY 1998 and 

FY 1999, NIAID and NIDDK established this cooperative research program to evaluate the 

safety and efficacy of promising tolerance induction treatment regimens in nonhuman 

primate models of kidney and islet transplantation. The knowledge gained from this research 

effort will be critical to moving tolerance induction strategies into clinical trials. 

• Immunological Phenotyping of Mouse Mutants. In FY 1999, the National Center for 

Research Resources (NCRR) joined NIAID, NEI, NIEHS, NHLBI, NIDDK, and ORWH to 

cosponsor the development of new technologies for rapid immunologic screening of normal 

and mutagenized mice. These efforts will enable the detection and characterization of 

abnormal immune responses, with an emphasis on immune dysfunction associated with 

autoimmune diseases. 

• NIH Autoimmune Rat Model Repository and Development Center. This collaborative 

effort of multiple NIH Institutes organized by NIAMS and the NIH Office of Research 

Services’ Veterinary Resources Program will develop and make available to researchers 

genetically characterized and disease-free laboratory rats for autoimmune disease research. 

NURSING, BEHAVIORAL, AND HEALTH SERVICES RESEARCH—Quality of life can 

be severely compromised for those suffering from autoimmune diseases. The NIH supports a 

variety of unsolicited research, intervention, and education programs aimed at improving disease 

management and quality of life for patients with chronic illness, their families, and their 

caregivers. To promote the recruitment and development of health care professionals who treat 

patients with chronic illnesses, the NIH supports training programs and scientific and 

professional meetings in this area. 

• General Clinical Research Centers. The GCRCs, a NCRR-supported resource for clinical 

research, study the effect of stress, mood, and pain on disease pathology and develop new 

strategies to monitor disease activity and novel approaches for management of disease. 

Programs include Intensive Therapy for Youth with IDDM (insulin dependent diabetes 

mellitus) at Washington University, St. Louis, MO; Biobehavioral Model of Stress and 

Multiple Sclerosis at the University of Pittsburgh, PA; and Psychosocial Aspects of 

Scleroderma at the University of California, San Diego. 

• Adolescent Diabetes Control and Quality of Life Improved by Combining Intensive 

Diabetes Therapy With Coping Skills Training. Interventions to improve metabolic 

control and quality of life in children with diabetes are of critical importance to reduce or 

prevent the onset of a number of long-term complications, e.g., blindness, heart disease, 

stroke, kidney failure, amputations, and nerve damage. National Institute of Nursing 

Research (NINR)-funded research is determining whether a coping skills training program, in 

conjunction with intensive therapy, will enhance quality of life, increase metabolic control 

(which is extremely difficult to control in diabetic children), and reduce adverse diabetes 

events in adolescents. An NIH clinical trial has shown that intensive diabetes therapy can 

reduce the number and severity of diabetes complications in adolescents and young adults. 

11 
RESEARCH RESOURCES—Research resources include support for the training of basic and 

clinical researchers and a broad range of equipment and infrastructure needs. 

• JDFI Islet Production Network. The JDFI supports seven institutions in the United States 

and Western Europe to produce islet cells for research. As part of the Foundation’s 

cosponsorship of the Immune Tolerance Network, islets for clinical trials in transplantation 

for type 1 diabetes are being provided to qualified Network investigators. 

• NIAID Repository of Transgenic and Gene-Targeted Mutant Mice. NIAID supports a 

repository of genetically manipulated mice and provides for the importation, verification, 

cryopreservation, breeding, and distribution of novel strains of transgenic or gene knockout 

mice for use by the extramural research community. This resource includes mouse models 

relevant for preclinical studies of autoimmunity. 

• NIAID MHC Tetramer Core Facility. In FY 1998, NIAID established a national facility to 

provide researchers with peptide-MHC tetrameric molecules for analyzing antigen-specific T 

cell responses. This methodology replaces and greatly improves upon cumbersome, 

insensitive, and time-consuming assays. Furthermore, by centralizing the production of 

these tetramers, reagents can be produced economically and can be made available to 

investigators at greatly reduced costs. Because T cells are central to virtually all adaptive 

immune responses, this technology is applicable to studies in many areas, including 

autoimmune disorders. 

• New Imaging Technologies for Autoimmune Diseases. Under the leadership of NIAID, 

with cosponsorship of multiple NIH Institutes, a FY 1999 research initiative was started to 

develop new methods of in vivo imaging of the immune system in small animal models of 

human autoimmune diseases. The development of high-resolution imaging technologies will 

provide new, powerful, noninvasive methods to visualize ongoing normal and deleterious 

immune responses. Further adaptation of high-resolution imaging for use in humans holds 

promise for noninvasive detection, diagnosis, and monitoring of immunologic diseases and a 

new approach for evaluating the efficacy of therapies and vaccines. 

• Imaging Pancreatic Beta Cell Mass, Function, or Inflammation. The NIDDK is 

sponsoring an initiative in FY 2000 to stimulate the development of techniques or reagents 

leading to the ability to image or otherwise noninvasively detect pancreatic beta cells in vivo 

and measure their function, mass, or evidence of inflammation. 

• Transplant Registries. NIAID, NCI, and NHLBI support the International Bone Marrow 

Transplant Registry (IBMTR) and the Autologous Blood and Marrow Transplant Registry 

(AMBTR). The IBMTR/ABMTR have collected data on blood cell and bone marrow 

transplantation for more than 20 years from more than 290 institutions worldwide. Studies 

address questions regarding short- and long-term outcomes in defined patient groups, 

relevant prognostic factors, the efficacy of different transplant approaches, and the economic 

impact of bone marrow transplantation. Both registries serve as a national resource for 

patients and patient advocacy groups, physicians, researchers, and the NIH. These registries 

have been collecting data on stem cell transplants performed for autoimmune diseases since 

early 1998. 

12 
• Pancreas Transplant Registry. Supported by the NIDDK, this registry at the University of 

Minnesota has collected data on nearly 10,000 pancreas transplants from more than 200 

institutions. Based on analysis of data from the registry, the Health Care Financing 

Administration and some third-party payors now cover the costs of pancreas transplants for 

individuals who are also undergoing kidney transplant as a result of diabetes. 

• Specialized Centers of Research (SCOR). Currently, NIAMS SCORs are targeted for RA, 

SLE, and scleroderma, among other diseases. A SCOR brings together basic and clinical 

researchers to provide mutually supportive research interactions to (1) advance basic research 

on disease causation and (2) expedite transfer of these advances into clinical applications and 

improved patient care. Present studies at the SCORs include a focus on the genetics of SLE 

and scleroderma. 

SCIENTIFIC SYMPOSIA, WORKSHOPS, AND PUBLICATIONS 

NIH Institutes, Centers, and Offices cosponsor a variety of scientific, programmatic, educational, 

and informational activities, often in collaboration with non-Federal partners. Recent (FY 1999 

and FY 2000) examples include: 

• Infectious Etiologies of Chronic Diseases. This workshop focused on causative roles for 

infectious agents in chronic disease, e.g., herpes and human papilloma viruses in Kaposi’s 

sarcoma and cervical cancer, respectively. Workshop participants evaluated preliminary data 

implicating additional agents in chronic disease, including autoimmune diseases, and 

identified key components and resource needs of a targeted research effort for future 

discovery of such agents. (NCI, NIAID) 

• Discovery of Human Immune Response Genes. This workshop focused on resource needs 

(e.g., patient and normal control cohorts, registries, DNA repositories, cDNA, sequencing 

and bioinformatics capabilities) to identify, characterize, and determine the functions of 

novel genes involved in autoimmune disorders. [NIAID, NIH Office of Rare Diseases 

(ORD)] 

• Linking Environmental Agents and Autoimmune Diseases. This workshop defined the 

state of the art, future directions, and research needs to understand the mechanistic links 

between environmental agents and development or exacerbation of autoimmune diseases. 

[NIEHS, NIAMS, NIAID, NIDDK, ORD, ORWH, Environmental Protection Agency, JDFI, 

American Autoimmune Related Diseases Association (AARDA)] 

• Basic Research Conference of the American College of Rheumatology. For the second 

year, this meeting has been cosponsored by NIAMS and NIAID. The focus of the 1999 

conference, which had a record attendance of approximately 600 participants, was the basic 

biology of B cells and their role in autoimmune diseases. 

• New Immunotherapies for Autoimmune Diseases. This unique, dual-track symposium 

highlighted research advances and opportunities in autoimmune diseases for a combined 

audience of lay and scientific participants. [NIAID, NIEHS, NIAMS, NIDDK, NINDS, 

13 
ORWH, ORD, AARDA, JDFI, Arthritis Foundation (AF), Crohn’s & Colitis Foundation of 

America (CCFA), Myositis Foundation, Sjogren’s Syndrome Foundation, National 

Pemphigus Foundation] 

• Institute of Medicine (IOM) Study on Safety of Silicone Breast Implants. In 1997, 

Congress expressed concerns about fragmentation of research on the safety and health effects 

of silicone and instructed the Department of Health and Human Services (DHHS) to 

commission an IOM expert review of research on the association of silicone implants with 

“autoimmune-like” syndromes (http://www.nap.edu/books/0309065321/html/). (NIAMS, 

NCI, NIAID, ORWH, FDA Office of Women’s Health, CDC, DHHS Office of Public Health 

and Science, DHHS Office of the Assistant Secretary for Science Policy and Evaluation) 

• Second Annual Arthritis Research Conference. This conference brings together the NIH 

and privately supported trainees and their mentors to highlight ongoing research in 

rheumatologic diseases. (NIAMS, NIAID, AF, American College of Rheumatology) 

• Workshop on Accelerated Atherosclerosis in Systemic Lupus Erythematosus. The goals 

of the conference were to (1) identify and establish potential interventions aimed at reducing 

mortality and morbidity from accelerated atherosclerosis in SLE and (2) identify research 

opportunities to establish the pathogenesis of accelerated atherosclerosis in SLE. (NIAMS, 

NHLBI) 

• Neuropsychiatric Manifestations of Systemic Lupus Erythematosus. The goals of the 

meeting were to (1) address current conceptual and evaluative tools in rheumatology, 

neurology, psychiatry, and psychology and their applications to the problem of nervous 

system involvement in SLE and (2) identify research opportunities using the approaches and 

tools described for the purpose of facilitating diagnosis and treatment of patients with 

neuropsychiatric manifestations of SLE. (NIAMS) 

• Gene Therapy Approaches for Diabetes and Its Complications. This workshop assessed 

the current understanding of the pathogenesis of diabetes and its complications and identified 

strategies that use gene therapy to intervene in the induction and progression of diabetes. 

Investigators described their results using gene therapy approaches to treat diabetes in both 

animal models and patients. (NIDDK, NCRR, NIAID, NHLBI, JDFI, ADA) 

• Stem Cells and Pancreatic Development. The objective of this workshop is to bring 

together investigators from multiple disciplines doing state-of-the-art research in stem cell 

biology and developmental biology of the pancreas to develop methods for stimulating 

growth or regeneration of beta cells. (NIDDK, ADA, JDFI) 

III. OPPORTUNITIES 

In the 21st century, there will be unprecedented opportunities to understand autoimmune 

diseases at the molecular and genetic levels. A major goal of NIH research in this area is to 

forge a conceptual and mechanism-based understanding that emphasizes features shared among 

these disorders. This will enable scientists and clinicians to more rapidly translate new 

knowledge into more effective treatments for a wide range of autoimmune diseases. Many of 

14 
these opportunities are outlined in detail in the strategic plans of the individual NIH Institutes 

located on the World Wide Web (http://www.nih.gov). Individually, these plans pave the way 

for significant scientific and clinical advances in selected areas, many of which are outlined 

below. Taken together, the continued success of these efforts will require leadership at the 

Federal level and a high degree of coordination at the NIH. 

To begin to address these needs, in November 1999, members of the Autoimmune Diseases 

Coordinating Committee established nine workgroups to foster scientific collaborations and to 

develop research initiatives in the following areas: (1) vaccines for autoimmune diseases, (2) 

functional genomics of autoimmunity, (3) gender and autoimmunity, (4) autoimmunity across 

the lifespan, (5) environment’s role in autoimmunity, (6) neuropsychiatric manifestations of 

SLE, (7) clinical registries for autoimmune diseases, (8) basic and clinical research in 

scleroderma, and 9) ankylosing spondyloarthropathies. Opportunities in several of these and 

other highly promising areas are outlined in the sections that follow. 

IMMUNE TOLERANCE 

Tolerance induction is a major therapeutic goal for the three major disease-related areas of 

modern immunology: autoimmunity, transplantation, and allergy/asthma. Furthermore, 

understanding the basic processes that control immune recognition will facilitate new approaches 

to augment protective immunity, including the design of improved vaccines. Thus, findings 

generated from this research will be highly relevant to many NIH components. In autoimmunity, 

efforts to induce tolerance have focused largely on oral administration of antigen. To date, it has 

not been possible to duplicate in humans several very encouraging studies of oral tolerance in 

animal models. Through the research programs described above, and in collaboration with 

industry, NIH-supported scientists are now poised to explore a variety of other promising 

approaches, including (1) costimulatory blockade, (2) T cell depleting recombinant 

immunotoxins, (3) small peptide inhibitors of T cell activation, (4) stem cell transplantation, and 

(5) gene transfer-based approaches for cytokine modulation. The development of improved 

animal models, including nonhuman primate models of autoimmune diseases, will be key to the 

success of these efforts. 

IMPROVED DIAGNOSIS AND PATIENT MANAGEMENT 

Autoimmune diseases present many complex challenges to the clinician. Prominent among these 

are the difficulties in establishing a diagnosis early in the course of disease and the lack of 

surrogate markers to monitor therapy and predict clinical outcomes. Thus, new tools are needed 

to ensure that the most promising experimental approaches will lead to better clinical outcomes. 

Examples include technologies for (1) whole body imaging and imaging immune activation at 

the cellular level in vivo; (2) tracking numbers and functional activation of antigen-specific 

immune cells; (3) staging disease, measuring responses to therapy, and predicting clinical 

outcomes; and (4) profiling disease susceptibility through low-cost, high-throughput, sensitive, 

and specific screening measures suitable for large-scale prevention trials. The NIH is providing 

the research infrastructures to support these endeavors through repositories, reagent facilities, 

and a wealth of recently initiated cooperative clinical programs. Examples of the latter include 

the Autoimmunity Centers of Excellence, the Immune Tolerance Network, Pilot Trials on 

Innovative Therapies for Rheumatic and Skin Diseases, Clinical Trials and Clinical Markers in 

15 
Immunologic Diseases, the Immunohistocompatibility Working Group, the Diabetes Prevention 

Trial—Type 1; and the proposed Diabetes TrialNet. 

GENETICS 

As the sequencing of the human genome approaches completion, it will be possible to define 

autoimmune diseases by focusing on individual genes and the proteins they encode. For 

example, it will be possible to rapidly, systematically, and at low cost determine the functional 

state of activation of immune cells and target tissues through a variety of DNA-based 

technologies, such as DNA microarrays. Similarly, advances in these technologies will enable 

rapid, low-cost profiling to measure the risks of developing disease in healthy individuals. A 

major challenge for the NIH will be to establish the bioinformatics capacity to link a variety of 

disease- and organ-specific databases for hypothesis generation and clinical profiling in a crossdisciplinary manner. A number of NIH Institutes are currently collaborating in this area. In 

particular, the Genetics Working Group of the Autoimmune Diseases Coordinating Committee is 

exploring options for a common autoimmune disease genetics database to facilitate data mining 

and identification of overlapping genetic regions controlling autoimmunity. The NIH currently 

supports the collection of clinical data and samples from families with various autoimmune 

diseases for use in research studies. Examples include the Multiple Autoimmune Disease 

Genetics Consortium, North American Rheumatoid Arthritis Consortium, Lupus Registry and 

Repository, and Juvenile Rheumatoid Arthritis Study. 

GENDER AND AUTOIMMUNITY 

Autoimmune diseases disproportionately affect women. For certain autoimmune diseases, 

incidence rates in females are 2 to 9 times higher than in matched male populations. Many of 

these diseases increase in frequency after puberty or flare during pregnancy, suggesting a role for 

sex hormones in their pathogenesis. Recent findings of increased numbers of long-lived cells of 

fetal origin in patients with certain autoimmune diseases, however, suggest the increased female 

incidence may be related to factors other than hormones. Thus, both hormonal and nonhormonal 

factors may contribute to gender-based differences in immune responses. 

NIAID sponsored a meeting on gender and autoimmunity and recently participated in a task 

force on sexual dimorphism in autoimmune disease organized by the National Multiple Sclerosis 

Society, the latter of which resulted in a major review article titled “A Gender Gap in 

Autoimmunity,” published in Science in 1999. The ORWH report titled “Agenda for Research 

on Women’s Health for the 21st Century: A Report of the Task Force on NIH Women’s Health 

Research Agenda for the 21st Century” highlighted the importance of determining the 

differences in the immune responses of men and women. Each of the groups recommended 

increased support for basic and clinical research on sex-based differences in the immune 

response. Recently, NIAID and the National Multiple Sclerosis Society have begun discussion 

of approaches to collaboratively target this important gap in our knowledge, to provide wider 

visibility of the problem and the opportunities, and to allow increased support for high-quality 

and relevant gender-based research. Other NIH Institutes, Centers, and Offices have expressed 

interest in this effort by joining the Autoimmune Diseases Coordinating Committee workgroup 

on gender and autoimmunity. 

16 
VACCINES FOR AUTOIMMUNE DISEASES 

The 1999 IOM report titled “Vaccines for the 21st Century” identified vaccines for autoimmune 

diseases as level-one priorities based on potential medical, social, and economic benefits to 

society. Vaccines for autoimmune diseases will be distinct from vaccines given to generate 

immunity to infectious agents. Instead, vaccines for autoimmunity will turn off a destructive 

immune response directed at the body’s own tissues. Although there are currently no vaccines 

against any autoimmune disease, successes in animal models and increased understanding of 

autoimmunity indicate the feasibility of developing preventive vaccines for these diseases. 

Distinct vaccines for each disease will likely be required. Whether general population 

vaccination or targeted vaccines based on genetic risk will be necessary, however, is not clear. 

NIAID, with its long history of vaccine development for infectious diseases, is aware of the 

extensive collaboration of academia, government, industry, and the public required for success. 

Through the Autoimmune Diseases Coordinating Committee, several Institutes and organizations 

are beginning to work toward this goal. 

INFECTIOUS AGENTS AND ENVIRONMENTAL FACTORS 

Because identical twins are not concordant for development of autoimmune disease, an 

environmental or infectious factor, in addition to genetic background, may be necessary. 

Multiple infectious agents have been suggested, but a definitive mechanism or association has 

been elusive. Recently, animal studies have elucidated several possible mechanisms, and human 

studies have focused on several particular agents. It is not likely that a single agent will be 

involved in each disease, but these new leads might elucidate the role of foreign organisms or 

compounds in the triggering of these diseases. This knowledge should lead to new approaches to 

treatment and prevention. 

IV. CONCLUSIONS 

The U.S. investment in biomedical research has yielded major advances in health and quality of 

life for Americans. However, each advance brings a new set of challenges. The major 

challenges facing research in autoimmune diseases today are (1) development of a mechanismbased, conceptual understanding of autoimmune disease; (2) translation of this knowledge into 

new, broadly applicable strategies for treatment and prevention of multiple diseases; and 

(3) development of sensitive tools for early and definitive diagnosis, disease staging, and 

identification of at-risk individuals. Through a wealth of individual, coordinated, and 

collaborative programs outlined in this report, NIH-supported scientists are vigorously pursuing 

these goals. 

17 
Appendix A 

AUTOIMMUNE DISEASES COORDINATING COMMITTEE ROSTER 

February 2000 

NIH Institutes, Centers, and Offices 

Elaine Collier, M.D. 

National Institute of Allergy and


Infectious Diseases


Susana A. Serrate-Sztein, M.D.


National Institute of Arthritis and


Musculoskeletal and Skin Diseases


Audrey Penn, M.D.


National Institute of Neurological


Disorders and Stroke


Hilary Sigmon, Ph.D., R.N.


National Institute of Nursing Research


Barbara B. Mittleman, M.D.


National Institute on Aging


A. Julianna Gulya, M.D.


National Institute on Deafness and Other


Communication Disorders


Ellen S. Liberman, Ph.D.


National Eye Institute


Barbara Linder, M.D., Ph.D.


National Institute of Diabetes and Digestive 

and Kidney Diseases 

Karen Winer, M.D. 

National Institute of Child Health and 

Human Development 

Kenneth A. Gruber, Ph.D. 

National Institute of Dental and Craniofacial 

Research 

John F. Finerty, Ph.D. 

National Cancer Institute 

Robert Musson, Ph.D.


National Heart, Lung, and Blood Institute


Dianne Rausch, Ph.D.


National Institute of Mental Health


Jerry Robinson, Ph.D.


National Center for Research Resources


Jeffrey Trent, Ph.D. 

National Human Genome 

Research Institute 

Jagjitsingh H. Khalsa, Ph.D. 

National Institute on Drug Abuse 

Kathleen Michels, Ph.D. 

Fogarty International Center 

Pamela Marino, Ph.D. 

National Institute of General Medical 

Sciences 

Steven K. Akiyama, Ph.D. 

National Institute of Environmental Health 

Sciences 

Calbert A. Laing, Ph.D.


Center for Scientific Review


Vivian Pinn, M.D.


Office of Research on Women’s Health


Stephen C. Groft, Pharm. D.


Office of Rare Diseases


Federal Agencies 

Jeffrey N. Siegel, M.D. 

FDA/Center for Biologics Evaluation 

and Research 

18 
Sahar M. Dawisha, M.D. 

FDA/Center for Devices and Radiological 

Health 

Kent Johnson, M.D. 

FDA/Center for Drug Evaluation 

and Research 

Robert F. Ashman, M.D. 

Department of Veterans Affairs 

Patricia W. Mueller, Ph.D. 

Centers for Disease Control 

and Prevention 

Private Organizations 

Virginia Ladd/Stanley M. Finger, Ph.D. 

American Autoimmune Related Diseases 

Association 

Stephen C. Reingold, Ph.D. 

National Multiple Sclerosis Society 

John H. Klippel, M.D. 

Arthritis Foundation 

Robert A. Goldstein, M.D., Ph.D.


Juvenile Diabetes Foundation International


Lloyd Mayer, M.D.


Crohn’s and Colitis Foundation of America


Margaret Dowd


The S.L.E. Foundation


Jane Salmon, M.D.


American College of Rheumatology


Janice Wherry, M.D., Ph.D.


Pharmaceutical Research and Manufacturers


of America


Katherine Morland Hammitt


Arthur I. Grayzel, M.D., M.A.C.R.


Elaine Alexander, M.D., Ph.D.


Sjogren’s Syndrome Foundation


Richard Kahn, Ph.D.


American Diabetes Association


19 
Appendix B 

AUTOIMMUNE DISEASES COORDINATING COMMITTEE 

MISSION STATEMENTS 

NIH Institutes, Centers, and Offices 

The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports 

research to elucidate the etiopathology of all autoimmune diseases and to develop new 

approaches to prevent and treat these immune-mediated diseases. 

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 

conducts and supports research into the causes, treatment, and prevention of autoimmune 

components of rheumatic and skin diseases, the training of basic and clinical scientists to carry 

out this research, and the dissemination of information on research progress in these diseases. 

The National Cancer Institute (NCI) conducts and supports autoimmunity research in 

paraneoplastic syndromes, in which autoimmune diseases are symptoms of an underlying 

malignancy, and in the deliberate induction of tumor-specific autoimmune responses for 

immunotherapeutic approaches to the treatment and cure of cancer. 

The National Institute of Child Health and Human Development (NICHD) conducts and 

supports research in the prevention and treatment of type 1 diabetes and in the reproductive 

sciences including premature ovarian failure of autoimmune etiology and uterine changes that 

occur in women with autoimmunity. 

The National Institute on Deafness and Other Communication Disorders (NIDCD) conducts 

and supports research in the impact of autoimmune diseases on hearing, balance, smell, taste, 

voice, speech, and language. 

The National Institute of Dental and Craniofacial Research (NIDCR) conducts and supports 

research in autoimmune diseases of the oral cavity, such as Sjogren’s syndrome. 

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has broad 

interests in the area of autoimmunity and autoimmune diseases, including endocrine diseases, 

such as type 1 diabetes and thyroiditis; digestive track and nutritional diseases, such as 

inflammatory bowel disease, celiac disease, primary biliary cirrhosis, and other autoimmune 

liver diseases; and kidney and blood/bone diseases, such as glomerulonephritis. A new “joint” 

branch within NIDDK, the Navy/NIDDK Transplant and Autoimmunity Branch, will study 

autoimmune pathogenesis of type 1 diabetes and perform translational research leading to islet 

transplants for type 1 diabetics. 

The National Institute on Drug Abuse (NIDA) supports more than 85 percent of the world’s 

research on health aspects of drug abuse and addiction. It also supports research on infections, 

including HIV/AIDS, and associated medical and health consequences, including 

immunosuppression in drug users. Research areas within NIDA’s mission include the effects of 

20 
drug abuse in patients with rheumatoid arthritis, diabetes-related metabolic disorders, lupus, and 

other autoimmune disorders. 

The National Institute of Environmental Health Sciences (NIEHS) conducts and supports 

research to elucidate the role of environmental factors in the etiopathology of autoimmune 

diseases. 

The National Eye Institute (NEI) conducts and supports autoimmunity research in 

immunosuppression, tolerance, anterior chamber associated immune deviation, ocular 

complications from autoimmune diseases, and autoimmune uveitis. 

The National Heart, Lung, and Blood Institute (NHLBI) supports investigations of the 

contribution of autoimmunity to diseases under its purview and in transfusion medicine and the 

use of autoimmune reagents and responses in disease diagnosis, treatment, and prevention. 

The National Institute of Mental Health (NIMH) conducts and supports research in the 

contribution of central nervous system autoimmunity to the development of neuropsychiatric and 

behavioral disorders, such as autism, bulimia nervosa, and pediatric autoimmune 

neuropsychiatric disorders (PANDAS). 

The National Institute of Neurological Disorders and Stroke (NINDS) conducts and supports 

research in autoimmune disorders of nerve and muscle such as multiple sclerosis, acute and 

chronic neurodegenerative diseases involving inflammatory mechanisms, and the impact of 

autoimmunity on the blood-brain barrier. 

The National Institute of Nursing Research (NINR) supports research to establish a scientific 

basis for the care of individuals across the lifespan—from management of patients during illness 

and recovery to the reduction of risks for disease and disability and the promotion of healthy 

lifestyles. Research extends to problems encountered by patients, families, and caregivers and 

emphasizes the special needs of at-risk and underserved populations. Autoimmunity research 

aims to develop strategies to promote self-management, cope with chronic illness, promote 

adherence to treatment, and prevent complications in conditions such as diabetes, rheumatoid 

arthritis, and irritable bowel syndrome. 

The Fogarty International Center (FIC) promotes international cooperation in biomedical 

sciences by encouraging collaboration between U.S. and foreign scientists. 

The National Center for Research Resources (NCRR) provides a comprehensive range of 

resources and technologies to support biomedical research. Scientists use these resources to 

better understand, prevent, and treat autoimmune diseases. 

The Office of Research on Women’s Health (ORWH) works with the NIH Institutes and 

Centers to ensure that NIH-supported research focuses on issues important to women’s health, to 

ensure that women and minorities are included in NIH-supported clinical research, and to 

enhance career opportunities for women in biomedical research. 

21 
Federal Agencies 

The U.S. Food and Drug Administration (FDA) regulates biological products, including blood, 

vaccines, therapeutics, and related drugs and devices, according to statutory authorities; assures 

that safe and effective drugs are available to Americans; ensures the safety and effectiveness of 

medical devices; and eliminates unnecessary human exposure to man-made radiation from 

medical, occupational, and consumer products. 

The Office of Research and Development at the U.S. Department of Veterans Affairs (VA) 

National Headquarters improves the effectiveness, efficiency, and accessibility of health care 

services for veterans by supporting research on the pathology, diagnosis, and treatment of 

autoimmune diseases. 

Private Organizations 

The American Autoimmune Related Diseases Association (AARDA) is a nonprofit 

organization that fosters and facilitates collaboration in education, public awareness, research, 

patient services, information dissemination, and research in all autoimmune diseases. 

The American College of Rheumatology (ACR), a nonprofit organization of physicians, health 

professionals, and scientists, advances rheumatology through programs of education, research, 

and advocacy and fosters excellence in the care of people with rheumatic and musculoskeletal 

diseases. 

The Crohn’s and Colitis Foundation of America (CCFA) is a nonprofit research organization 

that seeks the cause of and cure for Crohn’s disease and ulcerative colitis, collectively known as 

inflammatory bowel disease. 

The National Multiple Sclerosis Society (NMSS), a nonprofit organization, researches the cause and 

impact of MS and seeks to identify effective preventions, treatments, and a cure for this disease by 

obtaining and applying scientifically gathered basic, clinical, and health services knowledge. 

The Sjogren’s Syndrome Foundation is a nonprofit organization that educates patients, their 

families, the public, and healthcare providers about Sjogren’s syndrome and encourages research 

for new treatments and a cure for this disease. 

The Systemic Lupus Erythematosus Foundation, a non-profit organization, seeks the cause, 

improved treatment, and a cure for lupus by funding medical research and providing services to 

assist patients, families, and friends. 

22 
Appendix C 

FY 1999 AUTOIMMUNITY RESEARCH INITIATIVES 

Initiative Title Cosponsors 

23 

Autoimmunity Centers of Excellence NIAID*, NIDDK, ORWH, NIAMS 

Clinical Trials and Clinical Markers for Immunologic 

Diseases 

NIAID 

Environment/Infection/Gene Interaction in Autoimmunity NIEHS, NIAID, NIDDK, NIAMS, NICHD, NIDC

NINDS, NIMH, NIDCR, ORWH 

Human Immunology Centers of Excellence NIAID 

Human Islet Transplantation into Humans NIDDK, NIAID, JDFI 

Hyperaccelerated Award/Mechanisms in Immune Disease 

Trials 

NIAID, NIAMS, NIDDK, NINDS, NHLBI, ORW

Immune Tolerance Network: Autoimmune Disease NIAID, NIDDK, JDFI Immunological Phenotyping of Mouse Mutants NIAID, NCRR, NEI, NHLBI, NIDDK, NIEHS, OR

Multiple Autoimmune Disease Genetics Consortium 

(MADGC) 

NIAID, NIAMS, NHLBI, NIDDK, NICHD, NIDC

New Imaging Technologies for Autoimmune Disease NIAID, NCI, NCRR, NEI, NHLBI, NIAMS, NIDC

NIMH, NINDS, ORWH 

Nonhuman Primate Models of Transplantation Tolerance NIAID, NIDDK, NCRR 

Pilot Trials on Innovative Therapies for Rheumatic and Skin 

Diseases 

NIAMS, NIAID, NICHD, ORWH 

Rat Autoimmune Disease Genetic Resource NIAMS, NIAID, NHLBI, NIDCR, NIDDK, NCRR

Stem Cell Transplantation for Treatment of Autoimmune 

Diseases 

NIAID, NHLBI, NIDDK, NIDCR, NICHD, ORW

Supplements to NIAMS Registries and Repositories NIAMS 

Target Organ Damage in Autoimmune Disease NIAMS, NIAID, NIDCR, NIDDK, NICHD, NIEH

NHLBI, NINDS, NIMH, ORWH 

*Bold indicates the lead Institute.
Appendix D


NIH-Sponsored Initiatives in Autoimmune Diseases Research


FY 1996 to FY 2001


Initiative Supporting Institute(s) and Organizations FY 

Innovative Grants on Immune Tolerance NIAID, NIDDK 2001–2003 

Specialized Centers of Research (SCORs) in 

Osteoporosis, Rheumatoid Arthritis, and 

Scleroderma 

NIAMS 2001–2005 

Multidisciplinary Clinical Research Centers for 

Arthritis and Musculoskeletal and Skin Diseases 

NIAMS 2001–2005 

Transitional Career Development Award in Women’s 

Health Research 

NIA, NIAID, NIAMS, NCI, NICHD, NIDCR, 

NIDA, NIEHS, NHLBI, NIMH, NINDS, NINR, 

ORWH, PFIZER 

2001–2004 

Skin Diseases Research Core Centers NIAMS 2001–2005 

Rheumatic Diseases Core Centers NIAMS 2001–2005 

Hyperaccelerated Award/Mechanisms in 

Immunomodulation Trials 

NIAID, NIA, NIAMS, NIDDK, NHLBI, NINDS, 

ORWH 

2000–2004 

New Strategies for the Treatment of Type 1 

Diabetes 

NIDDK NIAID, NICHD 2000–2002 

Innovative Research in Human Mucosal Immunity NIAID, NIDCR, CCFA 2000–2001 

High-Risk Arthritis and Musculoskeletal and Skin 

Diseases Research 

NIAMS 2000–2001 

Prevalence and Diagnosis of Celiac Disease NIDDK 2000–2004 

Mechanisms of Chondroprotection NIAMS 2000–2004 

Diabetes Centers of Excellence NIDDK, NIAID, JDFI 2000–2004 

Clinical Trials and Clinical Markers for Immunologic 

Diseases 

NIAID 2000–20004 

Immune Tolerance Network NIAID, NIDDK, JDFI 1999–2006 

Immunological Phenotyping of Mouse Mutants NIAID, NCRR, NEI, NHLBI, NIDDK, NIEHS, 

ORWH 

1999–2000 

New Imaging Technologies for Autoimmune 

Diseases 

NIAID, NCI, NCRR, NEI, NHLBI, NIAMS, 

NIDCR, NIDDK, NIMH, NINDS, ORWH 

1999–2003 

Multiple Autoimmune Diseases Genetics 

Consortium 

NIAID 1999–2004 

Clinical Trials in Stem Cell Transplantation for 

Autoimmune Diseases 

NIAID 1999–2004 

Rat Autoimmune Model Repository NIAMS, NIAID 1999–2003 

Pilot Trials on Innovative Therapies for Rheumatic 

and Skin Diseases 

NIAMS, NIAID 1999–2003 

Nonhuman Primate Transplant Tolerance 

Cooperative Study Group 

NIAID, NIDDK, NCRR 1999–2003 

Target Organ Damage in Autoimmune Diseases NIAMS, NIAID, NIDCR, NIDDK, NICHD, 

NIEHS, NIDCD, NEI, NHLBI, NINDS, NIMH, 

ORWH 

1999–2003 

Human Rheumatic Disease Registries NIAMS 1999 

Pilot Studies for New Therapies for Type 1 Diabetes 

and Its Complications 

NIDDK, NIAID, NCRR, NHLBI, NIDCR, 

NICHD, NEI 

1999–2000 

Human Islet Transplantation Into Humans NIDDK, NIAID, JDFI 1999–2003 

Environment/Infection/Gene Interactions in 

Autoimmune Disease 

NIEHS, NIAID, NIDDK, NIAMS, NICHD, 

NIDCD, NEI, NHLBI, NINDS, NIMH, NIDCR, 

ORWH 

1999–2001 

Autoimmunity Centers of Excellence NIAID, NIDDK, NIAMS, ORWH 1999–2002 

Hyperaccelerated Award/Mechanisms in Immune 

Disease Trials 

NIAID, NIAMS, NIDDK, NINDS, NHLBI, 

ORWH 

1999–2003 

Human Immunology Centers of Excellence NIAID 1999–2002 

24
Appendix D


NIH-Sponsored Initiatives in Autoimmune Diseases Research


FY 1996 to FY 2001


(continued)


Initiative Supporting Institute(s) and Organizations FY 

Specialized Centers of Research (SCORs) in 

Osteoporosis, Rheumatoid Arthritis, and 

Scleroderma 

NIAMS 1998/1999– 

2002/2003 

Immunopathogenesis of Type 1 Diabetes NIDDK, NIAID, NICHD 1998–2000 

Cellular and Molecular Approaches to Achieving 

Euglycemia 

NIDDK, NCRR, NIAID, NICHD, NIA 1998–2000 

Thrombocytopenia: Pathogenesis and Treatment NHLBI 1998–2002 

Transplantation Tolerance NIAID, NIDDK 1998–2001 

Specialized Centers of Research (SCORs) in 

Osteoarthritis and Systemic Lupus Erythematosus 

NIAMS 1997/1998– 

2000/2001 

Diabetes Interdisciplinary Research Programs NIDDK, NIAID, JDFI 1997–2001 

Autoimmunity: Genetics, Mechanisms, and 

Signaling 

NIAID, NIAMS, NIDDK, NIA, ORWH 1997–2003 

Mucosal Immunity in Pathogenesis/Prevention of 

Human Disease 

NIAID, NIHLBI, NIA, NIAMS, NIDCD, NIDR, 

NIDDK, ORWH 

1996–2003 

Cellular and Molecular Mechanisms of Diabetic 

Cardiomyopathy 

NHLBI, NIDDK, NIA 2000-2002 

Role of Microbes in Autoimmune and ImmuneMediated Diseases NIAID, NINDS, NIAMS 1996–2003 

Gender in the Pathogenesis of Autoimmunity: 

Mechanisms 

NIAID, NIAMS, NINDS, NIDDK, NIDR, 

ORWH 

1996-2003 

Mechanisms Underlying Immunotherapy Trials in 

Autoimmunity 

NIAID, NIDDK, NIAMS, ORWH 1996–2000 

Interdisciplinary Programs in Autoimmune Disease NIAID, NIDDK, JDFI 1996–1999 

Mucosal and Synovial Gene Transfer in 

Infection/Inflammation 

NIAID, NIAMS 1996–2000 

25
Appendix E 

LIST OF ABBREVIATIONS AND ACRONYMS 

AARDA American Autoimmune Related Diseases Association


ADA American Diabetes Association


AF Arthritis Foundation


AMBTR Autologous Blood and Marrow Transplant Registry


AS Ankylosing spondylitis


ATD Autoimmune thyroid disease


CCFA Crohn’s and Colitis Foundation of America


CDC Centers for Disease Control and Prevention


FDA U.S. Food and Drug Administration


GCRC General Clinical Research Center


IBD Inflammatory bowel disease


IBMTR International Bone Marrow Transplant Registry


IHWG International Histocompatibility Working Group


IOM Institute of Medicine


JDFI Juvenile Diabetes Foundation International


JRA Juvenile rheumatoid arthritis


MHC Major histocompatibility complex


MS Multiple sclerosis


NCI National Cancer Institute


NCRR National Center for Research Resources


NEI National Eye Institute


NHLBI National Heart, Lung, and Blood Institute


NIAID National Institute of Allergy and Infectious Diseases


NIAMS National Institute of Arthritis and Musculoskeletal and Skin Diseases


NICHD National Institute of Child Health and Human Development


NIDCD National Institute on Deafness and Communication Disorders


NIDCR National Institute of Dental and Craniofacial Research


NIDDK National Institute of Diabetes and Digestive and Kidney Diseases


NIEHS National Institute of Environmental Health Sciences


NIH National Institutes of Health


NIMH National Institute of Mental Health


NINDS National Institute of Neurological Disorders and Stroke


NINR National Institute of Nursing Research


ORD Office of Rare Diseases


ORWH Office of Research on Women’s Health


RA Rheumatoid arthritis


SLE Systemic lupus erythematosus


VA U.S. Department of Veterans Affairs


26