Hypogammaglobulinemia and common variable immune deficiency

Hypogammaglobulinemia and common variable immune deficiency (CVID) are heterogeneous primary immunodeficiencies, first described more than 50 years ago. Hypogammaglobinemia is characterized reduced serum immune globulins due to a low IgG. CVID is defined by a low serum IgG with other isotype defects, as well as poor to absent antibody production (Picard et al., 2018 and Seidel et al., 2019). These disease syndromes are clinically heterogenous, with diverse age of onset of symptoms and disease manifestations ranging from infections, to complex phenotypes of immune dysregulation. While the cardinal feature of CVID is a prominent humoral immune defect, patients have numerous additional cellular defects. While long considered as a genetic defect, only in the past decade have some of the complex genetic underpinnings of the CVID syndrome been elucidated. Although there are clearly kindreds with CVID, IgA deficiency and/or hypogammaglobulinemia, these conditions are distinct and likely have variations on the pathophysiologic drivers of disease.