Detection and Characterization of Host Defense Defects

Study Overview
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Brief Summary
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This protocol is designed to evaluate selected patients with documented recurrent or unusual infections and their family members for clinical and laboratory correlates of immune abnormalities. It allows long term follow up of patients with host defense defects and permits the periodic study of their blood, urine, saliva, skin, stool and vaginal specimens or wound drainage from such patients or their family members for medically indicated purposes and research studies related to understanding the genetic and biochemical bases of these diseases. This protocol may help provide patients and materials for the development of therapies for these diseases. This study will: Determine the biochemical and genetic causes of inherited immune diseases affecting phagocytes (white blood cells that defend against bacterial and fungal infections) Try to develop better ways to diagnose and treat patients with these diseases, and to prevent, diagnose and treat their infections Patients and family members may undergo the following procedures: A personal and family medical history, physical examination and other procedures, which may include various blood tests; urinalysis; saliva collection; imaging studies such as chest X-ray, computed tomography (CT) or magnetic resonance imaging (MRI); and lung function studies, dental examination or eye examinations, if medically indicated. Patients who have draining wounds will have fluid collected from these wounds for biochemical study. Tissues removed as part of medical care, such as pieces of lung, liver, or teeth, or biopsies of these tissues will be studied. Patients who have an immune problem that investigators wish to study further will be asked to return to NIH for follow-up visits at irregular intervals, but at least every 6 months. The visits will include an updated medical history, examination directed at the particular medical problem related to the immune disorder, follow-up of abnormal tests or treatment, and collection of blood, saliva, urine, or wound fluid for study. Patients may have genetic testing and must be willing to have specimens stored for future research. Family members will have a medical history, saliva or urine collection, and chest X-ray or other imaging study, if medically indicated. Normal volunteers who have had tissue biopsies or pieces of tissue removed as part of medical care, such as pieces of lung, liver, or teeth, will have these tissues studied. NIH does not cover the cost of the initial screening visit for travel or lodging. A financial assessment may determine if the patient is eligible for financial assistance. This study does not enroll children under the age of 2. Patients will be asked to obtain their medical records, previous test results, or imaging studies prior to the first visit.

Detailed Description
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This protocol is designed to evaluate selected patients with documented recurrent or unusual infections and their family members for clinical and in vitro correlates of immune abnormalities. It will also allow long term follow up of patients with host defense defects and permit us to periodically obtain blood, urine, saliva, skin, other excess biopsy tissue, breast milk, stool and vaginal specimens or wound drainage from such patients or their family members for medically indicated purposes and research studies related to understanding the genetic and biochemical bases of these diseases. This protocol may help provide patients and materials for the development of therapies for these diseases in the future.

Official Title
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Detection and Characterization of Host Defense Defects

Conditions
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Immune Defects

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Patients known to have or suspected of having an immune defect significantly or primarily involving the phagocytes will be eligible for enrollment, as well as their blood relatives. Such syndromes include but are not limited to those listed above. Eligibility will not be limited based on sex, race, or disability. Patients or patient relatives must be over 1 month of age. The patient and patient relative cohorts will include the following special populations: Children: Children are included in this study because immune defects may present in early childhood, and early diagnosis or characterization may benefit subjects. Decisionally impaired adults: Patients and patient relatives will be able to provide informed consent for themselves or if they lack the capacity to provide informed consent, the study team will obtain consent from the legally authorized representative. Patients with underlying immune disorders, autoimmune phenomena or severe infections may sometimes present with delirium, encephalopathy, or coma and are therefore unable to provide informed consent. Excluding patients who are unable to provide consent could adversely impact patient access to medical therapy at the NIH as well as adversely impact research recruitment. Excluding patients unable to provide consent would also essentially prohibit us from evaluating patients at higher risk for adverse outcomes and therefore skew our understanding of disease. Similarly, enrolled patient subjects who lose the ability to provide ongoing consent during study participation may continue in the study. The risks and benefits of participation for subjects unable to consent should be identical to those described for less vulnerable patients. The process for obtaining consent for these individuals is described below. Healthy volunteers will be healthy adults between the age of 18 and 80 years of either sex, and they must be able to provide informed consents for themselves. EXCLUSION CRITERIA: The presence of an acquired abnormality which leads to immune defects, such as HIV, cytotoxic chemotherapy or malignancy, could be grounds for possible exclusion if, in the opinion of the investigator, the presence of such disease process interfered with evaluation. Individuals with dementia that impairs obtaining informed consent are excluded from enrolling as healthy volunteers, although such subjects may enroll in the patient or relative cohorts if consent can be obtained as described below.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Volunteer<br>Healthy Volunteer to serve as controls | |
| Patient<br>Patients known to have or suspected of having an immune defect significantly or primarily involving the phagocytes | |
| Patient Relatives<br>blood relatives of patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved disease if either normalization or sustained improvement is observed. | The primary endpoint of this study will be determination of a discrete diagnosis of an infecting agent, an underlying susceptibility trait, or both. | Complete withdrawal from steroid or sustained reduction to low dose antimicrobials or immune modulators. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Deficiency, Infection, Phagocytes, Cytokines, Genetics, Natural History