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
Rheumatology 2019 March 8

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.


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