B cells, autoimmunity, and innate immunity in 22q11.2 deletion syndrome: a two-center study and review of the literature.

INTRODUCTION: A few studies have reported that 22q11.2 del syndrome (DiGeorge syndrome - DGS) is associated with alterations in B-lymphocytes and innate immunity that predispose to infections and autoimmunity. The present study investigated the B-cell compartment, autoimmunity markers, and components of innate immunity, including NK cells, NK-specific cytotoxicity, phagocytic functions, and adhesion molecules. MATERIAL AND METHODS: Thirty-five DGS patients and twenty healthy controls were evaluated. Nephelometric, flow cytometric, ELISA and immunofluorescence techniques were used. RESULTS: There was no significant difference between the study and control groups regarding gender and age. Serum IgG, IgM levels and percentages, and antibodies against vaccine antigens were significantly lower in DGS patients. In DGS patients, 57.2% had low levels of non-switched memory B-cells, and 22.8% had low values of switched memory B-cells. Immature transitional B-cells, immature B-cells, plasmablasts, and active B-cells were significantly elevated. Autoantibodies were found positive in between 2.9% and 14.3% in the patient group. Natural killer T (NKT) cells and regulatory T cells (Tregs) were significantly decreased, whereas Fas+ active cytotoxic cells and Fas+ naive T helper cells were significantly elevated in DGS patients. NK-specific cytotoxicity was found to be higher in the patient group. CONCLUSIONS: Defects in humoral immunity, including immunoglobulin deficiencies and decreases in class-switched and nonclass-switched memory B-cell compartments, were common in DGS patients. While decreased Treg and NKT cells play a role in the increased incidence of autoimmunity, increased Fas+ cells counteract autoimmunity. Based on all these data, we would like to emphasize the importance of monitoring DGS patients for immune dysregulation.