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Common Variable Immunodeficiency

by James Fernandez, MD, PhD

Common variable immunodeficiency (acquired or adult-onset hypogammaglobulinemia) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but do not develop into Ig-producing cells.

Common variable immunodeficiency (CVID) includes several different molecular defects, but in most patients, the molecular defect is unknown. Mutations are sporadic in > 90% of cases. CVID is clinically similar to X-linked agammaglobulinemia in the types of infections that develop, but onset tends to be later (typically between ages 20 and 40). T-cell immunity may be impaired in some patients.

Patients have recurrent sinopulmonary infections. Autoimmune disorders (eg, autoimmune thrombocytopenia, autoimmune hemolytic or pernicious anemia, SLE, Addison disease, thyroiditis, RA, alopecia areata) can occur, as can malabsorption, nodular lymphoid hyperplasia of the GI tract, granuloma formation, lymphoid interstitial pneumonia, splenomegaly, and bronchiectasis. Gastric carcinoma and lymphoma occur in 10% of patients.

Diagnosis

  • Measurement of serum Ig and antibody titers

  • Flow cytometry for T-cell and B-cell subsets

  • Serum protein electrophoresis

Diagnosis is suggested by recurrent sinopulmonary infections and requires all of the following:

  • Low (at least 2 standard deviations below the mean) levels of IgG

  • Low levels of IgA, IgM, or both

  • Impaired response to immunizations (usually both protein and polysaccharide vaccines)

  • Exclusion of other immunodeficiency disorders

Antibody levels should not be measured if patients have been treated with IV immune globulin (IVIG) within the previous 6 mo because any detected antibodies are from the IVIG.

B-cell and T-cell quantification by flow cytometry is done to exclude other immunodeficiency disorders and to distinguish CVID from X-linked agammaglobulinemia, multiple myeloma, and chronic lymphocytic leukemia; findings may include low-numbers of class switched memory B cells or CD21+ cells. Serum protein electrophoresis is done to screen for monoclonal gammopathies (eg, myeloma), which may be associated with reduced levels of other Ig isotypes.

Spirometry, CBC, liver function tests, and a basic metabolic panel are recommended yearly to check for associated disorders. If lung function changes, CT should be done.

Because mutations are usually sporadic, screening relatives is not recommended unless there is a significant family history of CVID.

Treatment

  • Prophylactic IVIG once/mo

  • Antibiotics for infections

Treatment consists of IVIG 400 mg/kg once/mo and antibiotics as needed to treat infection. Rituximab, TNF-α inhibitors (eg, etanercept, infliximab), corticosteroids, and/or other treatments may be required to treat complications such as autoimmune disorders, lymphoid interstitial pneumonia, and granuloma formation.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ENBREL
  • RITUXAN
  • REMICADE

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