Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

Abstract

IntroductionThe aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM).MethodsSerum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist).ResultsAnti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease.ConclusionsAnti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed.

Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients

“…Immunoprecipitation of all samples was performed to determine the presence of myositis-specific and -associated autoantibodies, as previously described 5,6 . The presence of anti-HMGCR was determined in all samples by ELISA using recombinant antigen, as previously described 7 .…”

The Clinical Features of Myositis-Associated Autoantibodies: a Review

“…Clinical findings are similar to adult counterparts with characteristic cutaneous lesions including ulcerations, arthritis, and milder muscle or amyopathic disease. Both chronic ILD and RP-ILD are prevalent especially the latter in the Asian population, making anti-MDA5 an important serological marker in children, as parenchymal lung disease is generally uncommon in JDM [37,44,45].…”

“…AutoAb targeting a cytoplasmic protein, first termed CADM-140 and subsequently identified as melanoma differentiation gene 5, was first described in Asian cohorts and more recently in US and European adult and juvenile studies [11,[35][36][37][38][39]. Anti-MDA5 autoAb defines a specific dermatopulmonary syndrome, but within this, it is evident that Asian and Caucasian patients differ implying genetic and environmental factors influence the phenotype.…”

Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease

“…56,57 Conversely, in a European cohort, anti-MDA5 was found in 7% of JDM and was associated with skin and mouth ulceration, arthritis and milder muscle disease but was not associated with RP-ILD similar to American adults. 58 Anti-MDA5-positive patients have distinctive features not only in physical manifestations but also in blood tests and radiological findings. Hepatobiliary enzymes and serum ferritin levels were elevated more often in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients and serum ferritin levels correlated with the activity of ILD in anti-MDA5-positive patients.…”