hypogammaglobulinemia

Hypogammaglobulinemia is a group of disorders characterized by abnormally low levels of immunoglobulins in the blood, most notably IgG, and often IgA and IgM. The reduced antibody levels compromise humoral immunity and increase susceptibility to recurrent bacterial infections, especially of the sinopulmonary tract, as well as certain enteric and systemic infections. The term encompasses both primary (inherited) and secondary (acquired) forms.

Primary forms arise from defects in B cell development or antibody production. They include X-linked agammaglobulinemia (Bruton) due to BTK mutations; common variable immunodeficiency (CVID); and various Ig class or B cell–signaling defects. Secondary hypogammaglobulinemia results from conditions such as protein-losing states (nephrotic syndrome, enteropathy), malnutrition, certain medications (immunosuppressants, rituximab), HIV infection, or hematologic malignancies. Some patients may present with isolated IgG deficiency or selective antibody production defects.

Diagnosis relies on immunoglobulin measurements showing low levels of IgG (often with reduced IgA and/or IgM), assessment of specific antibody responses to vaccines, and exclusion of secondary causes. B cell enumeration by flow cytometry and, when indicated, genetic testing can help identify a primary immunodeficiency. Evaluation typically includes a thorough infection history and monitoring for associated autoimmune or lymphoproliferative complications.

Management centers on immunoglobulin replacement therapy, delivered intravenously or subcutaneously at regular intervals to restore protective IgG levels. Antibiotics are used to treat bacterial infections; vaccination strategies should be individualized, with inactivated vaccines generally recommended and live vaccines avoided in certain contexts. Ongoing monitoring addresses infection frequency, IgG trough levels, and potential complications. Prognosis improves with appropriate Ig replacement, though the condition is usually lifelong and requires multidisciplinary care.

Epidemiology varies by type; primary hypogammaglobulinemias are rare and collectively represent a minority of primary immunodeficiencies, whereas secondary forms occur in broader clinical settings.