Diagnostic potential of sarcoplasmic myxovirus resistance protein A expression in subsets of dermatomyositis

Abstract

To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analysing different DM subforms, and to test the superiority of MxA to other markers. Immunohistochemistry for MxA and retinoic acid-inducible gene I (RIG-I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti-Mi-2 (n=6), -transcription intermediary factor 1 gamma (n=10), -nuclear matrix protein 2 (n=13), -melanoma differentiation-associated gene 5 (MDA5) (n=10) or -small ubiquitin-like modifier activating enzyme (n=1) autoantibodies and with no detectable autoantibody (n=17). Among the patients, nine suffered from cancer and 22 were juvenile-onset type. Disease controls included antisynthetase syndrome (ASS)-associated myositis (n=30), immune-mediated necrotizing myopathy (n=9) and inclusion body myositis (n=5). Sarcoplasmic MxA expression featured 77% sensitivity and 100% specificity for overall DM patients, while RIG-I staining and PFA reached respectively 14% and 59% sensitivity and 100% and 86% specificity. In any subset of DM, sarcoplasmic MxA expression showed higher sensitivity than RIG-I and PFA. Some anti-MDA5 antibody-positive DM samples distinctively showed a scattered staining pattern of MxA. No ASS samples had sarcoplasmic MxA expression even though six patients had DM skin rash. Sarcoplasmic MxA expression is more sensitive than PFA and RIG-I expression for a pathological diagnosis of DM, regardless of the autoantibody-related subgroup. In light of its high sensitivity and specificity, it may be considered a pathological hallmark of DM per se. Also, lack of MxA expression in ASS supports the idea that ASS is a distinct entity from DM.