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National Institute of Allergy and Infectious Diseases | health information 

CEDS

What Is CEDS?

CEDS is a very rare genetic disorder 

of the immune system. CEDS stands 

for “caspase eight deficiency state.” 

The disorder is characterized by an 

enlarged spleen and lymph nodes, 

recurrent sinus and lung infections, 

recurrent viral infections, and a low 

level of infection-fighting antibodies. 

CEDS is diagnosed based on clinical 

and laboratory findings as well as 

genetic testing.

Genetics primer: All the cells in the body contain instructions on how to do 

their job. These instructions are packaged into chromosomes, each of which 

contains many genes, which are made up of DNA. Errors, or mutations, in the 

genes can cause diseases such as CEDS. Credit: NIAID

Genetics

CEDS is caused by mutations in the CASP8 gene, which 

provides instructions for production of the protein 

caspase eight, which is also abbreviated as CASP8. The 

CASP8 protein is involved in programmed cell death, 

or apoptosis. The body must maintain a careful balance 

between proliferation of immune cells and apoptosis 

to defend against pathogens and avoid autoimmunity. 

The mutations that cause CEDS destabilize the CASP8 

protein and block its function, leading to buildup of 

immune cells.

In this example, two unaffected parents each 

carry one copy of a gene mutation for an 

autosomal recessive disorder. They have one 

affected child and three unaffected children, two 

of which carry one copy of the gene mutation. 

Credit: U.S. National Library of Medicine

Inheritance

CEDS is inherited in an autosomal recessive manner. 

This means that affected people have a mutation on each 

of their two copies of CASP8—one inherited from their 

mother and one from their father. Sometimes the two 

copies have mutations that are identical, or homozygous. 

This often involves parents who are related to each other. 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Institute of Allergy and Infectious Diseases
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Alternatively, the mutations in each copy of the CASP8 gene are different. These are called compound 

heterozygous mutations.

In either case, parents of a child with CEDS are usually “carriers,” meaning they have one mutated 

copy of CASP8 and one normal copy. Carriers typically do not experience any symptoms of CEDS 

and lack immune-function abnormalities.

Clinical Symptoms

CEDS is related to autoimmune lymphoproliferative syndrome and used to be called ALPS type IIB. 

Although CEDS and ALPS share problems with apoptosis, CEDS is different from ALPS because 

of its additional immune deficiency symptoms. The symptoms of CEDS include splenomegaly 

(an enlarged spleen), lymphadenopathy (enlarged lymph nodes), recurrent sinopulmonary (sinus 

and lung) infections, recurrent mucocutaneous herpesvirus infections, persistent warts, molluscum 

contagiosum, and hypogammaglobulinemia (low antibody levels). Although immune cells called 

lymphocytes sometimes infiltrate certain organs, such as the lungs, liver, and kidneys, autoimmune 

problems are minimal. Lymphoma, a type of cancer, has not been observed in CEDS patients. 

However, people with ALPS are at increased risk of developing lymphoma.

Laboratory Findings

Doctors may perform immunologic studies to look for features that suggest CEDS. For example, they 

may assess serum immunoglobulin, or antibody, levels; antibody function; and lymphocyte activation. 

Patients with CEDS have hypogammaglobulinemia and develop poor antibody responses to certain 

vaccines. In addition, their immune cells, including B cells, T cells, and NK cells, do not activate 

well in response to stimuli.

Prognosis and Treatment

Given the rarity of CEDS, the prognosis for and optimal treatment of people with this condition

remain unclear. People with CEDS have done well while taking intravenous immunoglobulin and

prophylactic acyclovir, an antiviral drug, to prevent sinopulmonary infections and mucocutaneous

herpesvirus outbreaks. Investigators at the National Institute of Allergy and Infectious Diseases, part 

of the National Institutes of Health, are conducting clinical studies to identify new approaches for 

the diagnosis and treatment of this disorder. More information can be found on clinicaltrials.gov, 

using the study identifiers NCT00246857 and NCT00001467.

CEDS and Your Family

Living with CEDS can be difficult not only for the person who has it but for their family members 

as well. It is important for families to talk openly about CEDS and about how the family is dealing 

with it so misconceptions can be corrected and children can learn to cope with their reactions. 

Some children with CEDS have to work hard to develop their self-confidence and sense of security. 
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NIAID

Everyone benefits from being reminded that they have many positive characteristics, but this

is especially important when a child’s appearance attracts attention (for example, due to large

lymph nodes).

Some children who have siblings with the disease feel anxious about their brother or sister being in 

pain or even dying from the disease. Some think that they may develop symptoms because they look 

or act like a sibling who has the disease or that the disease is contagious. Some children struggle with 

how much time their parents spend with their sick sibling. Many families benefit from meeting or

talking to other families affected by the same rare disease. Patient organizations such as the Immune 

Deficiency Foundation (www.primaryimmune.org) are also great resources for providing useful 

information and support. Counseling can also help families cope with the challenges of CEDS.

At the same time, many families say that the disease has brought them closer together. Through

their experiences with the disease and its treatment, family members learn about controllable and 

uncontrollable aspects of life. Although certain aspects of the disease cannot be controlled, how a

family responds to the stress of any illness is controllable and an important aspect of managing CEDS.

Children also learn who they can turn to for support and how to solve problems. Acknowledging

both the challenges and opportunities that CEDS presents helps children develop resilience.
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NIAID

Glossary

Apoptosis—Programmed cell death, an important part of a 

healthy immune system.

Autoimmunity—A process during which a person’s immune 

system attacks healthy cells, organs, and tissues.

B cells—Immune cells that present antigens to T cells and 

produce antibodies, or immunoglobulins.

Cell—The basic unit of living organisms. Human cells consist of 

a nucleus (control center) and cellular organs, called organelles, 

enclosed by a membrane. Groups of cells with similar structure 

and function form tissues.

Chromosome—A thread-like structure made up of DNA that is 

tightly coiled around supporting proteins. Chromosomes reside 

in the control center, or nucleus, of a cell. 

DNA (deoxyribonucleic acid)—A self-replicating material 

present in nearly all living organisms. It is the carrier of genetic 

information.

Gene—A unit of heredity that is transferred from parent to child. 

Genes are made up of DNA. 

Hypogammaglobulinemia—A type of immune deficiency that 

is characterized by a reduction in all types of gamma globulins, 

or infection-fighting antibodies.

Immune system—A system of biological structures and processes 

within the body that protects it against “foreign” threats such as 

bacteria or viruses.

Lymphadenopathy—Enlarged lymph nodes.

Lymphocytes—A class of white blood cells that are part of the 

immune system.

Lymphoma—A type of cancer that occurs when certain immune 

cells start dividing uncontrollably and no longer behave like 

normal immune cells.

Molluscum contagiosum—A viral skin infection that results in 

round, firm, painless bumps.

Mucocutaneous herpesvirus—An infection of the skin or mucus 

membranes (mouth, nose, eyes, genitals) with herpesvirus.

Mutation—A change in the DNA sequence that is associated 

with disease or susceptibility to disease.

NK cells—Small lymphocytes that are part of the first line of 

immune defense. 

Phenotype—A person’s observable characteristics.

Proliferation—The rapid reproduction of cells.

Sinopulmonary infections—Infections of the sinuses and/or 

lungs.

Splenomegaly—Enlarged spleen.

T cells—Lymphocytes produced or processed by the thymus 

(a small organ located in the upper chest under the breastbone) 

that are actively involved in the immune response.

July 2015

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