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

Abstract

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 <or=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.

Figure 1

Sex-specific differences in CVID. CVID females (n=62) had higher numbers of switched memory and IgM-only memory B cells and higher baseline levels of IgA and IgM than males (n=43).

Figure 2

Memory B cells and antibody responses. Box plots showing response to protein and polysaccharide (Ps) antigens and A) switched memory B cells; B) serum IgG; and C) serum IgA levels. Vaccine responses were considered as: patients who do not respond to either protein antigens or Ps antigens, labeled as “No resp protein/Ps” in the figure; patients who respond to either protein antigens or Ps antigens or “Single resp Protein/Ps”, and patients who respond to both protein antigens and Ps antigens, or “Both resp Protein/Ps”. Each box plot reprsents the median (thick band) and the 25th and 75th centiles. The error bars represent the smallest and largest values that are not outliers.