Humoral Immunodeficiencies: Conferred Risk of Infections and Benefits of Immunoglobulin Replacement Therapy

Gernez, Yael; Baker, Mary Grace; Maglione, Paul J.

Primary immune deficiency diseases (PIDDs) result from genetic defects of the immune system that increase patients’ susceptibility to infections. The types of infections that occur in PIDD patients are largely dictated by the nature of the immune deficiency, which can be defined by dysfunction of cellular or humoral defenses. An increasing number of PIDDs, including those with both cellular and humoral defects, have antibody deficiency as a major feature and can benefit from immunoglobulin replacement therapy as a result. In fact, the most common PIDDs worldwide are antibody deficiencies and include common variable immunodeficiency, congenital agammaglobulinemia, hyper IgM syndrome, specific antibody deficiency, and Good syndrome. While immunoglobulin replacement therapy is the cornerstone of treatment for the majority of these conditions, a thorough understanding of the specific infections for which these patients are at increased risk can hasten diagnosis and guide additional therapies. Moreover, the infection trends in some PIDD patients with profound defects of cellular immunity, such as autosomal dominant hyper IgE syndrome (Job’s/Buckley’s Syndrome) or dedicator of cytokinesis 8 (DOCK8) deficiency, suggest that select patients might benefit from immunoglobulin replacement therapy even if their immune deficiency is not limited to antibody defects. In this review, we provide an overview of the predisposition to infections seen in PIDDs that may benefit from immunoglobulin replacement therapy.