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
- 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.
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
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. 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.
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 hypogammaglobulemia associated with other related
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
Patient must agree to submit samples for storage or future studies
On investigator s discretion unaffected family members may be asked for the provision of
the blood specimen for clinical and research purposes.
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
Presence of other medical illnesses that would preclude individuals from undergoing routine
diagnostic testing or testing for immunologic features of immunodeficiency.