Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Antonio López-Vázquez,Beatriz Suárez-Álvarez,Marcos López-Hoyos,Rebeca Alonso-Arias,Umberto Volta,Lourdes Mozo,Carlos Bousoño,Eduardo Arranz,José Ramón Vidal-Castiñeira,Carlos López-Larrea,Luís Rodrigo

doi:10.1186/1741-7015-12-34

Abstract

BackgroundOverexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes.MethodsWe tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies.ResultsAntibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without.ConclusionsThe development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones.

Highlights

Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases
Anti-MHC class I polypeptide-related sequence A (MICA) autoantibodies are more prevalent in patients with celiac disease Our initial aim was to analyze anti-MICA antibodies in sera obtained from patients diagnosed with Celiac disease (CD) and from healthy controls
Our results demonstrated that these autoantibodies were associated with CD (41.5% in the CD group versus 8.2% in the autoimmune disease (AD) group; P

Summary

Introduction

Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. Its most typical characteristics are a strong genetic association with the human leukocyte Autoantibodies, especially those directed against the tissue transglutaminase (tTG) enzyme, commonly appear in CD [6]. These antibodies are very important in the diagnosis of CD, but their role in the pathogenesis of the disease remains controversial [7]. Other studies have shown that antitTG antibodies may play an important role in epithelial cell proliferation [9] and interfere with intestinal epithelial cell adhesion [10] These autoantibodies disturb angiogenesis and modulate vascular permeability in vitro [11,12]. These observations suggest that future approaches to the study of CD should take the role of humoral immunity into account

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