This study will determine whether people with common variable immunodeficiency (CVID) with
and without gastrointestinal (GI) symptoms have gut abnormalities (inflammation or loss of
function) and changes in immune system cells and chemicals in the blood and gut. People with
CVID have decreased levels of serum immunoglobulin IgG and IgA. Patients have sinus, lung and
other infections, and many also have stomach and intestinal problems, such as chronic
diarrhea, inability to absorb nutrition from food, and intestinal infections caused by
CVID patients with gastrointestinal symptoms 10 years of age and older may be eligible for
this study; CVID patients without gastrointestinal symptoms 18 years of age and older will be
enrolled as control subjects. Candidates will be screened with a review of their medical
records, a medical history and physical examination, HIV blood test, stool sample, and
hydrogen breath test. The breath test measures the amount of hydrogen in the breath after
drinking sugar water, showing the digestive effects of bacteria in the upper intestine.
Participants will be admitted to the NIH Clinical Center for several days to undergo the
- Medical history and physical examination
- Blood tests
- Urine and stool samples
- 48-hour stool fat collection measures the amount of undigested fat in the stool to
determine the ability of the gut to digest and absorb fat in the diet
- D-Xylose absorption test measures the ability of a sugar compound to travel across the
lining of the intestine to determine the ability of the gut to absorb nutrients
- Upper endoscopy a thin flexible lighted tube is advanced through the mouth to evaluate
the esophagus, stomach and beginning of the small intestine
- Lower endoscopy a thin lighted tube is advanced through the rectum to evaluate the colon
Identification of GI abnormalities associated with changes in immune response in CVID
patients will help in developing and testing new treatments for this disease.
Common variable immunodeficiency (CVID) is a clinically heterogeneous disorder characterized
by decreased serum immunoglobulin IgG and IgA levels. In addition to chronic or recurrent
sinopulmonary infections, many patients develop gastrointestinal manifestations that can be
disabling or fatal. Data suggest that these gut abnormalities have a primary immune basis,
implicating T cells primarily, and are not related to the infectious complications of CVID.
Currently there is no standard therapy for the associated gastrointestinal disease outside of
empiric nutritional intervention for weight loss and non-specific anti-diarrheal agents. In
addition there is no data about the prevalence of gastrointestinal abnormalities in CVID
patients who have no overt gastrointestinal symptoms.
The objectives of this study are to characterize the gastrointestinal abnormalities that
occur in CVID patients and correlate this with the immunophenotype and cytokine secretion of
peripheral blood and lamina propria lymphocytes and monocytes. CVID patients with
gastrointestinal symptoms of malabsorption/maldigestion and chronic diarrhea will be targeted
for study. We will also include a group of patients without gastrointestinal symptoms to
provide an estimate of background prevalence and severity of gut abnormalities. Subjects will
undergo a standard immunologic workup including peripheral blood lymphocyte marker
phenotyping and cytokine responses as well as tests of gastrointestinal absorption,
examination of gut histology by endoscopic biopsy, and measurement of gut mucosal cytokine
expression. Analysis variables will include clinical (weight, stool frequency, results of gut
absorption tests), laboratory (lymphocyte and cytokine assays), and gut abnormalities
(histology scores and specific lesions).
- INCLUSION CRITERIA:
Must have a verifiable diagnosis of common variable immune deficiency specifically a
decrease both in IgG and at least one other Ig isotype to below two standard deviations of
normal control levels.
Must be age 10 years old or older for patients with gastrointestinal symptoms or age 18
years or older in the absence of gastrointestinal symptoms.
Must be free of active sinopulmonary or other infection at time of enrollment.
Must have negative results on stool examination for culture of enteric pathogens
(Salmonella, Shigella, Yersinia, Campylobacter, Vibrio, E. Coli O157/H7), Clostridia
difficile toxin assay, enteric parasites and their ova (including Cryptosporidia,
Cyclospora, Microsporidia and Giardia (by stool EIA)).
Adults who are unable to provide initial or on-going consent may participate in this study.
Absence of other antibody deficiency states including X-linked agammaglobulinemia, hyper
IgM syndrome, selective deficiency of IgG subclass, and Ig heavy chain gene deletions.
Use of immunomodulating drugs within the following times prior to enrollment: daily
corticosteroids (4 weeks), azathioprine/6-MP, cyclosporine, methotrexate, or FK506 (3
months). The use of short-term or single dose corticosteroids as a pretreatment regimen for
IVIG is acceptable.
Positive test for anti-HIV.
Significant systemic or major disease including congestive heart failure, coronary artery
disease, cerebrovascular disease and pre-existing or recent onset CNS demyelinating
disorder, pulmonary disease, renal failure, organ transplantation, decompensated liver
disease, serious psychiatric disease, or malignancy that in the opinion of the investigator
would preclude successful endoscopic evaluation.
Pregnancy, to avoid endoscopies without a strictly therapeutic intent in this relatively
high risk population.