Detection and Characterization of Infections and Infection Susceptibility

This study will examine the causes of immune disorders affecting white blood cells, which defend against infections and will try to develop better means of diagnosis and treatment of these immune disorders.

Patients known to have or suspected of having increased susceptibility to infections and their blood relatives may be eligible for this study, at the discretion of the principal investigator. Patients and family members may undergo the following procedures:

• Personal and family medical history.
• Physical examination and blood and urine tests.
• Studies of breathing function (pulmonary function testing)
• Dental examination.
• Eye examination.
• Microscopic examination of saliva, wound drainage or tissues removed for medical reasons for cell, hormone or DNA studies.

In addition, patients may be asked permission for investigators to obtain their medical records, previous test results, or radiographic studies and to undergo imaging studies, such as a chest X-ray, CT scan or MRI scan.

This screening study is designed to evaluate patients with suspected or identified recurrent or unusual infections and their family members for clinical and in vitro correlates of exposure and susceptibility. It will allow for up to 2 visits to obtain blood, urine, saliva, stool, skin biopsy, or wound drainage from such patients or their family members for research studies related to understanding the nature of the infection as well as the genetic and biochemical bases of these diseases. Patients determined by initial evaluation to be of interest for additional study or treatment will be asked to provide consent for enrollment into an appropriate NIH follow-up study. The present study will enroll up to 1200 patients and family members over the next 10 years.

• Immune Disorders
• Chronic Granulomatous Disease
• Genetic Immunological Deficiencies
• Hyperimmunoglobulin-E Recurrent Infection Syndrome
• Recurrent Infections

• Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev. 2000 Dec;11(4):321-33. Review.
• Fleisher TA, Straus SE, Bleesing JJ. A genetic disorder of lymphocyte apoptosis involving the fas pathway: the autoimmune lymphoproliferative syndrome. Curr Allergy Asthma Rep. 2001 Nov;1(6):534-40. Review.
• Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999 Mar 4;340(9):692-702.

• INCLUSION CRITERIA:

PATIENTS:

1. Patients known to have, or suspected of having an infection susceptibility will be eligible for enrollment.
2. Patients with known or suspected infections will also be eligible in order to identify the microbiologic cause of the infection, identify the extent of infection, or determine the proper course of treatment. There will be no limit as to age, sex, race or disability.
3. Patients must have a primary physician outside of the NIH and may be required to submit a letter from their physician that documents their relevant health history.
4. The patient or the patient's guardian will be willing and capable of providing informed consent after initial counseling by clinical staff. Separate consent forms for all interventional procedures will be obtained after explanation of the specific procedure.
5. Women of childbearing potential, or who are pregnant or lactating, may be eligible. Interventions in pregnant or lactating women will minimize as much as possible risks to the fetus/infant but will follow state of art evaluation and therapy. Should a woman become pregnant or suspect she may be pregnant while participating in this study, she should inform the study staff and her primary care physician immediately.
6. Patients must agree to have blood and tissue stored for future studies of the immune system and/or other medical conditions.
7. Patients may be concurrently enrolled on other protocols as long as the Principal Investigator is informed.

HEALTHY BLOOD RELATIVES OF PATIENTS:

1. Healthy blood relatives of patients known to have or suspected of having an infection susceptibility will be eligible for enrollment only if they have a sick relative who is enrolled on this protocol as a patient.
2. There will be no limit as age, sex, race or disability.
3. Relatives or the minor relative's guardian must be willing and capable of providing informed consent after initial counseling by clinical staff.
4. Participating relatives agree to have blood stored for future studies of the immune system and/or other medical conditions.

EXCLUSION CRITERIA:

1. A well understood acquired abnormality which leads to infection susceptibility, such as HIV, cytotoxic chemotherapy, or active malignancy may be adequate explanation for the infection diathesis. These may be grounds for exclusion if, in the opinion of the investigators, the presence of such disease process interferes significantly with evaluation (applicable to patients and their blood relatives).
2. Severe or uncommon infections or syndromes often require highly specialized teams and institutions. Some referred cases will not be able to be handled appropriately at the NIH and may be deemed ineligible for admission, as determined by the Principal Investigator.