Common Variable Immunodeficiency, Hypogammaglobulinemia, and Specific Antibody Deficiency

Antibody deficiencies are a group of primary immune deficiencies caused by defects in B-cell development, B-cell activation, or antibody synthesis. Defects discussed in this chapter include common variable immunodeficiency (CVID), specific antibody deficiency (SAD), and hypogammaglobulinemia. Patients with isolated antibody deficiencies often have increased frequency or prolonged course of sinopulmonary infections. Chronic diarrhea, chronic lung disease, autoimmune disease, or lymphoproliferative disease can also complicate antibody deficiencies, especially CVID. The diagnosis of antibody deficiency is based upon clinical picture, total immunoglobulin levels, and functional immune response to vaccines. Patients with CVID have low IgG levels in combination with either low IgA or IgM levels. Patients with hypogammaglobulinemia have isolated low IgG levels, while patients with specific antibody deficiency have normal total immunoglobulin levels. Importantly, diagnoses of CVID, SAD, or hypogammaglobulinemia require evidence of impaired immune response to vaccines. First-line therapy for CVID is immunoglobulin (Ig) replacement therapy, while patients with SAD and hypogammaglobulinemia can be trialed on prophylactic antibiotics before undergoing Ig replacement therapy. With the introduction of Ig replacement therapy, there has been a decrease in infectious complications; however, noninfectious complications remain a cause for reduced survival in patients with CVID.