MDA5 autoantibody—another indicator of clinical diversity in dermatomyositis

Abstract

Allenbach and colleagues have recently reported for the first time the results of an intriguing study of the histopathologic, immunopathologic and gene expression differences in muscle biopsy tissue from adult dermatomyositis (DM) patients who do and do not have circulating MDA5 autoantibodies (anti-MDA5). Anti-MDA5 were originally identified in a clinically-defined subset of DM patients whose disease was expressed predominately in the skin for unusually long periods of time without accompanying muscle weakness [i.e., "clinically-amyopathic DM" (CADM)] and were at risk for acute, rapidly-progressive form of interstitial lung disease (ILD). As an academic dermatologist in the United States of America (USA) having a career-long interest in the CADM subset, I would like to share my perspective on the results of the work by Allenbach and colleagues and offer some suggestions for additional study in this area. But to do so most effectively, I first would like to review the clinical concept of CADM and its association with anti-MDA5 antibody production and a potentially-fatal form of (ILD).

Aberrant activation of the type I interferon system may contribute to the pathogenesis of anti‐melanoma differentiation‐associated gene 5 dermatomyositis

“…An example would be ‘anti‐MDA5 (melanoma differentiation‐associated gene 5) DM’. Patients with DM with anti‐MDA5 autoantibodies usually possess the unique clinical phenotype characterized by the typical cutaneous manifestations and mild or even no myopathy, but frequently complicated with interstitial lung disease (ILD) . The prevalence of ILD in anti‐MDA5 DM has been estimated to be 50–73% in European and U.S. cohorts, while it has been recorded at higher rates of up to 86–100% in large Asian cohort studies .…”

“…The prevalence of ILD in anti‐MDA5 DM has been estimated to be 50–73% in European and U.S. cohorts, while it has been recorded at higher rates of up to 86–100% in large Asian cohort studies . Rapidly progressive ILD (RPILD) with a fatal outcome is observed in a considerable proportion of patients with anti‐MDA5 DM, particularly in Asian populations . The outcome of anti‐MDA5 autoantibody‐associated ILD was reported to be much worse than that of anti‐aminoacyl‐tRNA synthetase (ARS) autoantibody‐associated ILD …”

Hypomyopathic Dermatomyositis Presenting with Idiopathic CD4 T-lymphocytopenia and Delayed Anti-MDA5 Positivity

“…It is highly associated with the development of interstitial lung disease (ILD) [5]. The anti-MDA5 antibody is postulated to develop via molecular mimicry, although the exact mechanism is not entirely understood [6]. This antibody portends a poor prognosis, and the ILD seen in these cases is often refractory to steroid and immunosuppressant therapy.…”

Efficacy and Safety of Tofacitinib for Immunemediated Inflammatory Rheumatic Diseases (Part Ii)

“…У 4 из 9 пациентов (44,4%), получавших ГК (20 мг/сут), в трех случаях удалось отменить ГК-терапию. Особый интерес представляют данные, касающиеся эффективности ТОФА при так называемом амиопатическом ДМ [72,74,77], ассоциирующемся с синтезом антител к MDA5 (antimelanoma differentiation-associated protein 5) и развитием быстропрогрессирующего интерстициального заболевания легких [83].…”