2020 年 37 巻 2 号 p. 123-128
Dermatomyositis (DM) is characterized clinically by myositis and a unique set of skin eruptions and myopathologically by perifascicular atrophy and capillary C5b–9 depositions. In DM muscles, a set of proteins known to be induced by type I interferon, including myxovirus resistance protein A (MxA), are expressed. Sarcoplasmic MxA on immunohistochemistry is highly specific and sensitive for DM, and thus a useful diagnostic marker. In addition, an increasing number of reports have been recently describing the efficacy of JAK inhibitors, which block the type I interferon pathway, in patients with refractory DM. Therefore, DM can be regarded as muscle type I interferonopathy. Five DM–specific autoantibodies (DMSA) so far identified are against : TIF1–γ, MDA5, Mi–2, NXP–2, and SAE. In our cohort, 97% of DM cases confirmed by the sarcoplasmic MxA expression on muscle biopsy had one of DMSAs, suggesting that DMSA is a surrogate marker of muscle type I interferonopathy. Apparently, each DMSA is associated with a relatively specific phenotype. For example, anti–TIF1–γ autoantibodies are associated with malignancy and anti–MDA with clinically amyopathic DM. This indicates that DM may well be further subclassified by DMSA.
Antisynthetase syndrome (ASS) is characterized by the presence of anti–aminoacyl t–RNA synthetases (ARS). So far, 10 anti–ARS antibodies have been identified, including Anti–Jo–1, PL–7, EJ, OJ, PL–12, and KS autoantibodies. ASS was previously classified as DM because patients typically develop skin rash such as mechanic's hand, in addition to myositis and chronic idiopathic lung disease. However, a recently proposed classification of idiopathic inflammatory myopathies (IIMs) based upon pathological and serological features, in addition to clinical information, includes ASS as a distinct subtype of IIM. Mounting evidence indicates the correlation between autoantibodies and phenotypes also in ASS. Anti–Jo–1, PL–7, EJ, OJ autoantibodies are more closely associated with myositis rather than interstitial lung disease while anti–PL–12, KS autoantibodies are more closely correlated with interstitial lung disease. ASS is pathologically characterized by perifascicular necrosis and perifascicular pathology. Perifascicular necrosis may superficially resemble perifascicular atrophy, however, MxA is not expressed in myofibers in ASS, indicating ASS and DM have different pathomechanisms. Of note, anti–OJ autoantibodies, which are seen in 27% of ASS patients who received muscle biopsy, cannot be detected by line blot assay or ELISA.