Anti-MDA5 antibodies in a large Mediterranean population of adults with dermatomyositis.

Moises Labrador-Horrillo,Miquel Vilardell-Tarres,Eva Balada,Ernesto Trallero-Araguas,Maria Angeles Martinez,Albert Selva-O'Callaghan,Cándido Juárez

doi:10.1155/2014/290797

Abstract

A new myositis-specific autoantibody directed against melanoma differentiation-associated gene 5 (anti-MDA5) has been described in patients with dermatomyositis (DM). We report the clinical characteristics of patients with anti-MDA5 in a large Mediterranean cohort of DM patients from a single center, and analyze the feasibility of detecting this autoantibody in patient sera using new assays with commercially available recombinant MDA5. The study included 117 white adult patients with DM, 15 (13%) of them classified as clinically amyopathic dermatomyositis (CADM). Clinical manifestations were analyzed, with special focus on interstitial lung disease and its severity. Determination of anti-MDA5 antibodies was performed by a new ELISA and immunoblot technique. In sera, from 14 (12%) DM patients (8 CADM), MDA5 was recognized by ELISA, and confirmed by immunoblot. Eight of the 14 anti-MDA5-positive patients (57.14%) presented rapidly-progressive interstitial lung disease (RP-ILD) versus 3 of 103 anti-MDA5-negative patients (2.91%) (P < 0.05; OR: 44.4, 95% CI 9.3–212). The cumulative survival rate was significantly lower in anti-MDA5-positive patients than in the remainder of the series (P < 0.05). Patients with anti-MDA5-associated ILD presented significantly lower 70-month cumulative survival than antisynthetase-associated ILD patients. Among the cutaneous manifestations, only panniculitis was significantly associated with the presence of anti-MDA5 antibodies (P < 0.05; OR: 3.85, 95% CI 1.11–13.27). These findings support the reliability of using commercially available recombinant MDA5 for detecting anti-MDA5 antibodies and confirm the association of these antibodies with RP-ILD in a large series of Mediterranean patients with DM.

Highlights

In 2005, Sato et al [1] identified a novel autoantibody recognizing a 140-kDa protein in patients with dermatomyositis (DM), in those with clinically amyopathic dermatomyositis (CADM)
The cut-off value for a positive result on enzyme-linked immunoassay (ELISA) was established at 0.188 absorbance units, which corresponded to 2 standard deviations above the mean value obtained for the 25 healthy controls
Two patients diagnosed with DM, 2 with PM, and 1 with systemic sclerosis (SSc) showed weak anti-melanoma differentiation-associated protein 5 (MDA5) reactivity by ELISA, which was not confirmed by immunoblot; these results were considered false positives

Summary

Introduction

In 2005, Sato et al [1] identified a novel autoantibody recognizing a 140-kDa protein in patients with dermatomyositis (DM), in those with clinically amyopathic dermatomyositis (CADM). The 140-kDa autoantigen, which was identified as melanoma differentiation-associated protein 5 (MDA5), is detected in 19% to 35% of the patients with DM. The presence of anti-MDA5 antibody-associated dermatopulmonary syndrome was described in the white population [7,8,9]. The main drawback to routine use of this antibody for clinical purposes is that its determination is limited to techniques that are only available in research laboratories, such as immunoprecipitation of radioactive-labeled protein [8] or enzyme-linked immunoassay (ELISA) using in-house fabricated recombinant proteins [12, 13]

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