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Original research
Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease
  1. Naoshi Nishina1,
  2. Shinji Sato2,
  3. Kenichi Masui3,
  4. Takahisa Gono4 and
  5. Masataka Kuwana4
  1. 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  2. 2Division of Rheumatology, Department of Internal Medicin, Tokai University School of Medicine, Isehara, Japan
  3. 3Department of Anesthesiology, Showa University Graduate School of Medicine School of Medicine, Shinagawa-ku, Tokyo, Japan
  4. 4Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan
  1. Correspondence to Masataka Kuwana; kuwanam{at}


Objectives To investigate whether the onset of polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD) is influenced by season and residence in the context of myositis-specific autoantibodies.

Methods For patients with PM/DM-associated ILD enrolled in a multicentre cohort, 365 and 481 patients were eligible for seasonal and geographical analysis, respectively, based on the availability of reliable clinical information. The patients were divided into three groups: (1) anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients, (2) anti-aminoacyl tRNA synthetase (anti-ARS) antibody-positive patients and (3) patients negative for those antibodies. Seasonality was assessed by the Rayleigh test. Distance from residence to the nearest waterfront was measured on Google Map and was compared between groups by the exact Wilcoxon rank-sum test.

Results In anti-MDA5-positive patients, the disease developed more frequently in October–March (p=0.03), whereas a seasonal relationship was not found in the remaining two patient groups. Residence at disease onset in anti-MDA5-positive patients was significantly closer to the waterfront, especially to freshwater, compared with that in anti-ARS-positive or anti-MDA5-/ARS-negative patients (p=0.003 and 0.006, respectively).

Conclusions Anti-MDA5-associated ILD occurred predominantly from October to March in individuals residing near freshwater, suggesting an environmental influence on the onset of this disease subset.

  • Rheumatoid arthritis
  • Dermatomyositis
  • Cytokines
  • Systemic sclerosis
  • Autoantibodies

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  • Contributors NN, SS, and MK conceived and designed the study; NN and KM analysed the data; SS, KM, TG, MK and JAMI investigators contributed data collection/analysis tools; and all authors wrote the paper.

  • Funding This work was supported in part by a research grant for intractable diseases from the Japanese Ministry of Health, Labour and Welfare. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests SS holds the patent for the anti-MDA5 antibody measurement kit; MK holds the patent for the anti-MDA5 antibody measurement kit and has received consulting fees, speaking fees and research grants from Abbvie, Actelion, Asahi Kasei, Astellas, Boehringer Ingelheim, Bayer, Chugai, Eisai, Corbus, CSL Behring, Janssen, MBL, Mitsubishi Tanabe, Mochida, Nippon Shinyaku, Novartis, Pfizer, Ono, Reata, Takeda, Teijin and UCB. The other authors have no conflict of interest.

  • Patient consent for publication Not required.

  • Ethical approval JAMI was approved by the Ethics Committee of the coordinating centre (Nippon Medical School, Tokyo, Japan; 26-03-434) and by individual participating centres.

  • Data sharing statement Data are available upon reasonable request.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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