Bethesda, Maryland 20892


This study will explore the cause of immunodeficiency in common variable immunodeficiency (CVI) and other related immunodeficiency syndromes IgA deficiency, hyper IgM syndrome, thymoma and agammaglobulinemia, hypogammaglobulinemia associated with Epstein-Barr infection, and others to better focus on how to correct the underlying defect. Patients with CVI and their family members may participate in this study. Family members must be between the ages of 18 and 85, in good health and weigh at least 110 pounds. Patients will receive standard medical care for their illness. Procedures may include a medical history and physical examination, routine blood tests, stool examination for infectious agents, lung function tests, chest and sinus X-rays. Treatment may include administration of immune serum globulin, antibiotics for infections, and anti-inflammatory drugs, if needed. In addition, patients may undergo the following: - Lymphapheresis: This procedure is done to collect large numbers of white blood cells (lymphocytes). Blood is collected through a needle in an arm vein, similar to donating blood. The blood is separated it into its components by centrifugation (spinning), the white cells are removed, and the rest of the blood (red cells, plasma and platelets) is returned to the body, either through the same needle or through another needle in the other arm. - Blood draw: Blood may be drawn through a needle in an arm vein (venipuncture). No more than 450 milliliters (15 ounces) of blood will be collected over a 6-week period from adults, and no more than 7 ml (1 1/2 teaspoons) per kilogram (2.2 pounds) of body weight in children over the same time period. - Lymph node biopsies: Lymph node biopsies will be done only if required for diagnostic purposes. Some of the biopsy tissue may be kept for research. Up to two lymph nodes may be removed during each procedure. For the procedure, a painkiller is injected into and beneath the skin in the biopsy area, and the node is removed surgically. The incision is closed using dissolving sutures (stitches) that do not require removal. The biopsy takes about 30 minutes. Patients will be hospitalized at least overnight for observation. - Intestinal biopsies: Endoscopy and gastrointestinal biopsy will be done only if there is evidence of malabsorption. Some of the biopsy tissue may be kept for research. Patients are pre-medicated to allay anxiety, but are fully conscious during the procedure. A flexible tube is inserted into the stomach or small intestine through the mouth. The tube allows the doctor to see the intestinal mucosa and to project the image onto a TV screen. At various places in the mucosal surface, small pieces of tissue are plucked out using a small space at the tip of the endoscope. The procedure takes 30 to 60 minutes. Some of the blood collected may be used for genetic tests. Some blood and tissue samples may be stored for future research labeled with a code, such as a number, that only the study team can link to the patient. Participating family members will provide a medical history, and their pulse, blood pressure and temperature will be taken. They will have 10 to 120 ml (1/3 to 4 ounces) of blood drawn from a vein in the arm. Blood samples may be taken on repeated occasions as long as the relative remains in the study. The blood will be used for research that may involve development of diagnostic tests for CVI, evaluation of the structure and function of normal blood cells for comparison with those of patients with CVI, and studies to try to determine possible genetic factors involved in susceptibility to CVI.

Study summary:

The purpose of this protocol is to carry out laboratory studies concerning the immunopathogenesis of Common Variable Immunodeficiency (CVI) and related primary humoral immunodeficiency diseases. Additionally, we aim to document and track the progression of known complications of this primary immunodeficiency. Complications associated with CVID include recurrent respiratory, and gastrointestinal bacterial infections, pulmonary insufficiency, nodular regenerative hyperplasia, lymphoid malignancy, and various autoimmune manifestations. Patients with CVI and related B Cell immunodeficiencies will be enrolled into this natural history study. Protocol procedures will include baseline measurements of and changes in lab and radiographic studies. First or second degree genetically related family members (limited to mother, father, siblings, grandparents, children, aunts, uncles and first cousins of an affected patient) may also be screened for clinical, in vitro and genetic correlates of immune abnormalities. Changes in the patients clinical state will be measured to determine the precursors of disease complications. This may lead to developments in improving preventive measures and novel treatment options for this population.


- INCLUSION CRITERIA: - Must have a verifiable diagnosis of common variable immune deficiency as defined by a decrease both in IgG and at least one other Ig isotype to below two standard deviations of normal control levels OR B cell immunodeficiencies related to CVI (defined as selective IgA deficiency, hyper IgM syndrome, thymoma and agammaglobulinemia, and hypogammaglobulinemia associated with Epstein-Barr virus infection) or hypogammaglobulinemia associated with other related immunodeficiencies - Must be 2 years old or greater. - Patients with repeated infections and suspected of having an immunodeficiency syndrome. - Patients must have a primary medical care provider as a criterion for inclusion into this study. - Patient must agree to submit samples for storage or future studies - On investigator s discretion unaffected family members (mother, father, siblings, children, grandparents, aunts, uncles, and first cousins) may be asked for the provision of the blood specimen for clinical and research purposes. - Patients and patient relatives of child-bearing potential, or who are pregnant or lactating, may be eligible and will only undergo tests and procedures, and/or receive medications for which data exists proven minimal risk to the fetus or child. Only diagnostic tests without radiographs will be performed, unless clinically necessary for the care of the patient. All patients must be willing to have blood stored for future studies and/or other research purposes, such as but not limited to the modification of cells into iPS cells. - Adults who are unable to provide initial or on-going consent may participate in this study. When questions arise regarding an adult s ability to provide their own initial or on-going consent, a consultation with the NIH Ability to Consent Assessment Team will be obtained to determine their capacity to consent. In the event that an adult is determined unable to provide initial or on-going consent an appropriate surrogate may provide permission (as per NIH policy M87-4). The subject has the right to discontinue participation or refuse participation in the study at any time without impact to any care or treatment being provided under any other NIH protocol or future participation of a protocol offered at the NIH. EXCLUSION CRITERIA: -Presence of other medical illnesses that would preclude individuals from undergoing routine diagnostic testing or testing for immunologic features of immunodeficiency.



Primary Contact:

Principal Investigator
Warren Strober, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)

Kimberly L Montgomery-Recht, R.N.
Phone: (301) 827-0038

Backup Contact:

Warren Strober, M.D.
Phone: (301) 496-6810

Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone: 800-411-1222

Site Status: Recruiting

Data Source:

Date Processed: November 18, 2019

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