Role of environmental factors in autoantibody production - importance of a detailed analysis in a small cohort

autoantibodies to cellular constituents are useful biomarkers associated with a certain diagnosis or clinical manifestations or both. Autoantibodies in polymyositis/ dermatomyositis (PM/DM) have been actively studied in recent years, and several myositis-specifi c antibodies (MSAs) have been newly described. In the previous issue of Arthritis Research & Th erapy, Muro and colleagues [1] reported a detailed epidemi o-logic analysis in central Japan on one of the recently described MSAs, anti-MDA-5 (melanoma diff erentia-tion-associated gene 5). Th is autoantibody was originally named anti-CADM-140 because of its association with clinically amyopathic DM (CADM) and the molecular size (approximately 140 kDa) of the target antigen [2]. Th e antigen was only recently identifi ed as MDA-5, a cytoplasmic viral RNA receptor with RNA helicase activity [3]. MDA-5 is a part of anti-viral innate immunity. Stimulation of MDA-5 by its ligand induces type I-interferon (I-IFN) production, and I-IFN also upregulates MDA-5. A strong association of anti-MDA-5 with CADM accompanying interstitial lung disease (ILD) was confi rmed in several independent studies [3,4]. ILD in this subset is often rapidly progressive and resistant to treatment, making the detection of anti-MDA-5 clinically important. Reports on anti-MDA-5 were limited to Japan and Korea until recently, when a study in the US confi rmed the presence of this specifi city [5]. MDA-5 as a target of autoantibodies in a subset of DM makes an attractive story because both viruses and I-IFN have been implicated in the pathogenesis of DM. Muro and colleagues [1] showed that, in recent years at their institute, an increasing prevalence of anti-MDA-5 in a subset of patients was more prevalent in small rural towns compared with large cities. Furthermore, clustering of anti-MDA-5-positive cases to certain years and geographical areas is documented. In fact, fi ve out of six and four out of four patients with anti-MDA-5 in 2002 and 2010, respectively, were from the two small areas along the Kiso River. Th ese clustering patterns are consistent with the role of environmental factors associated with a rural community or the river/water system (or both) in the development of anti-MDA-5-positive CADM cases. Among environmental factors in DM, ultraviolet (UV) exposure has been considered important since the percentage of DM within PM/DM and prevalence of anti-Mi-2 antibodies correlate with the UV index of the area [6]. In vitro upregulation of a major DM autoantigen, Mi-2, by UV exposure supports this idea. However, given the history and occupation …