Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease

Yoshinari Nakatsuka; Tomohiro Handa; Ran Nakashima; Kiminobu Tanizawa; Takeshi Kubo; Yuko Murase; Akihiko Sokai; Kohei Ikezoe; Yuji Hosono; Kizuku Watanabe; Shinsaku Tokuda; Kazuko Uno; Akihiko Yoshizawa; Tatsuaki Tsuruyama; Ryuji Uozumi; Sonoko Nagai; Kazuhiro Hatta; Yoshio Taguchi; Michiaki Mishima; Kazuo Chin; Tsuneyo Mimori; Toyohiro Hirai

doi:10.1093/rheumatology/kez065

Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease

Rheumatology (Oxford). 2019 Mar 8:kez065. doi: 10.1093/rheumatology/kez065. Online ahead of print.

Authors

Yoshinari Nakatsuka¹, Tomohiro Handa², Ran Nakashima³, Kiminobu Tanizawa⁴, Takeshi Kubo⁵, Yuko Murase⁴, Akihiko Sokai⁶, Kohei Ikezoe⁴, Yuji Hosono³, Kizuku Watanabe⁴, Shinsaku Tokuda⁴, Kazuko Uno⁷, Akihiko Yoshizawa⁸, Tatsuaki Tsuruyama⁹, Ryuji Uozumi¹⁰, Sonoko Nagai¹¹, Kazuhiro Hatta¹², Yoshio Taguchi¹³, Michiaki Mishima¹⁴, Kazuo Chin¹, Tsuneyo Mimori³, Toyohiro Hirai⁴

Affiliations

¹ Department of Respiratory Care and Sleep Medicine.
² Department of Advanced Medicine for Respiratory Failure.
³ Department of Rheumatology and Clinical Immunology.
⁴ Department of Respiratory Medicine.
⁵ Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, Kyoto.
⁶ Department of Respiratory Medicine, Takatsuki Red Cross Hospital, Osaka.
⁷ Louis Pasteur Center for Medical Research, Kyoto.
⁸ Department of Diagnostic Pathology.
⁹ Department of Drug and Discovery Medicine.
¹⁰ Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto.
¹¹ Kyoto Central Clinic Clinical Research Center, Kyoto.
¹² Department of Rheumatology.
¹³ Department of Respiratory Medicine, Tenri Hospital, Nara.
¹⁴ Saiseikai Noe Hospital, Osaka, Japan.

PMID: 30851107
DOI: 10.1093/rheumatology/kez065

Abstract

Objective: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD).

Methods: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed.

Results: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions.

Conclusion: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

Keywords: anti-ARS antibody; anti-MDA5 antibody; fibrosis; interstitial lung disease; matrix metalloproteinase; polymyositis/dermatomyositis.