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.
 Lindh E et al. (2008) AIRE regulates T-cell-independent B-cell responses through BAFF. Proc Natl Acad Sci U S A. Nov 25;105(47):18466-71.
 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
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.