Background Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive syndrome due to mutations in AIRE gene, characterized by autoimmune endocrinopathies and mucocutaneous candidiasis. It is accompanied by generation of serum auto-antibodies. Recently the selective susceptibility to C. albicans has been related to the presence of neutralizing IgG antibodies against IL-17F and IL-22. A T cell independent mechanism implicated in altered peripheral B cell selection, through increased cytokine B-cell activating factor of the TNF family (BAFF), has been proposed. This is of practical importance given the recent advances in immunotherapy targeting B cells in a growing number of autoimmune diseases.
Objectives To perform a detailed analysis of B cell subsets in a large cohort of APECED patients compared to age-matched controls, in order to better understand whether an intrinsic alteration in B cell compartment is present. B lymphocytes related cytokines (BAFF, IL-21) were also evaluated in patients’ sera and supernatant from monocytes derived dendritic cells (MoDCs).
Methods Flow cytometric analysis of B cell subsets was performed in 12 patients with APECED from Sardinia, Italy, and compared to age-matched controls. The cohort is characterized by early onset and diagnosis, clinical heterogeneity, the presence of a wide range of circulating autoantibodies to tissue-specific antigens and genetical homogeneity. The following B cell subsets were analysed: transitional, CD21low B cell subset, naïve, IgM memory, switch memory B cells and circulating plasmacells. Serum IL-21 and BAFF levels, and MoDCs supernatant were evaluated by ELISA assay.
Results APECED patients display with age a reduction of CD19+ peripheral B cells accompanied by a significant defect in immature-transitional B lymphocytes. Circulating CD21low as well as switch memory B lymphocytes are significantly increased in older patients. Circulating plasma cells are not significantly altered. Serum levels of BAFF as well as BAFF secretion by MoDCs upon IFN-γ stimulation were found increased. No significant difference in IL21 serum levels was observed.
Conclusions These data show for the first time a significant deregulation of B cells subsets in APECED patients, affecting principally two major subsets: immature transitional, completely absent in older patients and switched memory B cells. Concomitantly up-regulation of BAFF in the absence of functional AIRE was observed. Increasing the knowledge on B cells in APECED patients improves the comprehension of autoimmunity pathogenesis in immunodeficiency and may allow the exploration of the possible clinical efficacy of B cell targeted therapy.
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 Puel A et al. (2010) Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. Feb 15;207(2):291-7.
 Kisand K et al. (2010) Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med. 2010 Feb 15;207(2):299-308.
Disclosure of Interest None Declared