Memory B cells in common variable immunodeficiency: Clinical associations and sex differences

Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by impaired antibody responses, recurrent infections, inflammatory, autoimmune and malignancy-related conditions. We evaluated the relationship between memory B cell phenotype, sex, age at diagnosis, immunologic and clinical conditions in 105 CVID subjects from one medical center. Reduced numbers of switched memory B cells (cutoff ≤ 0.55% of B cells) were an independent risk factor of granulomas, autoimmune diseases and splenomegaly (p < 0.001). Not previously noted, CVID females had significantly more switched memory cells (p = 0.007) than males. Splenectomized subjects did not have fewer IgM memory B cells and these numbers were not related to the development of lung disease, as previously proposed. Lower baseline serum IgG was an independent predictor of pneumonia (p = 0.007) and severe infections (p = 0.001). We conclude that outcomes in CVID depend on an interplay of factors including sex, numbers of switched memory B cells, and baseline serum IgG and IgA levels.