Absence of some common organ-specific and non-organ-specific autoimmunity in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy

N Kluger,A Ranki,K Krohn

doi:10.1530/ec-12-0074

Abstract

BackgroundAutoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations of the autoimmune regulator (AIRE) gene, whose loss of function leads to the escape of self-reactive T cells from the thymus and autoimmunity. APECED patients typically develop tissue-specific autoantibodies and anti-cytokine antibodies. Consequently, various endocrine and non-endocrine autoimmune disorders appear. However, only a certain number of autoimmune diseases develop, while some common autoimmune conditions have not been reported or are seen only anecdotally.ObjectiveWe investigated the clinical manifestations and occurrence of antinuclear antibodies (AN-Abs) and antibodies against extractable nuclear antigens, citrullinated peptide, and transglutaminase in 24 patients and against bullous pemphigoid antigen 180 and desmogleins 1 (Dsg1) and Dsg3 in 30 patients of a Finnish cohort of APECED patients.ResultsDespite the loss of central tolerance, the autoantibodies investigated were not overrepresented among the APECED patients. None of the patients had a history of autoimmune connective tissue disease, rheumatoid arthritis, celiac disease, or autoimmune cutaneous bullous disorders. Altogether, 25% (6/24) had low-titer (1:80) AN-Abs. Two patients had anti-BP180 antibodies and two others had anti-Dsg3 antibodies without any cutaneous or mucosal symptoms. No anti-citrullinated peptide and anti-transglutaminase reactivity was found.ConclusionsThe mechanisms that drives tolerance to tissue autoantigens is not fully understood as even APECED patients, who are genetically prone to develop autoantibodies, are tolerant against some common autoantigens. The hypothesis that some of the anti-cytokine antibodies commonly found in APECED patients may be protective should be investigated in larger series.

Highlights

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, OMIM 240300) or autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations of the autoimmune regulator (AIRE) gene, whose loss of function leads to the escape of self-reactive T cells from the thymus and autoimmunity
APECED patients typically develop a variety of tissue-specific autoantibodies [10], which are predictive of the development of autoimmune diseases [3, 4] and anti-cytokine antibodies such as type 1 interferons (IFN) and Th17-related interleukins 17 (IL17) and IL22 [11, 12]

Summary

Introduction

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, OMIM 240300) or autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder. It is caused by loss-of-function mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21 (21q22.3) [1, 2, 3, 4]. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations of the autoimmune regulator (AIRE) gene, whose loss of function leads to the escape of self-reactive T cells from the thymus and autoimmunity. The hypothesis that some of the anti-cytokine antibodies commonly found in APECED patients may be protective should be investigated in larger series

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