Background Interstitial lung disease (ILD) and concomitant infectious diseases are the predominant causes of death in polymyositis/dermatomyositis (PM/DM). We have already reported that hypocapnea and ILD lesion in upper lung fields are independent prognostic factors. Micro RNA is a non-coding RNA, which has a certain function such as transcriptional regulation. miR-1 has been reported to be associated with myocyte differentiation and to decrease in muscle tissue from patients with inflammatory myopathies.
Objectives Here we investigated the association of serum miR-1 level with clinical course of PM/DM-associated ILD (PM/DM-ILD).
Methods We retrospectively analyzed clinical baseline, serum miR-1 level, initial therapeutic regimens, total amounts of PSL, clinical outcomes, and episode of infection of patient with PM/DM-ILD who had received initial treatment at six hospitals associated with Yokohama City University from 2003 to 2016. The serum miR-1 level was measured by quantitative real-time PCR.
Results One hundred sixteen (PM 22, DM 51, and clinically amyopathic DM 43) patients were included. The mean age was 56±15 years and 83 were female. As initial therapies, oral PSL, methylprednisolone (mPSL) pulse, intravenous cyclophosphamide (IVCY), and oral calcineurin inhibitor therapies were performed in 113 (97%), 80 (69%), 48 (41%) and 80 (69%), respectively. Forty-one patients had a serious infection at 51±38 days from initiation of immunosuppressants and 10 died of infections. Old age, low PaCO2 and albumin, high LDH and KL-6, high score of ILD, high initial dose of PSL, mPSL pulse, IVCY, calcineurin inhibitor and combination therapy were extracted as risk factors for infection by univariate analyses. A multivariate logistic regression analyses revealed that combination therapy (p=0.012, OR 2.83), old age (p=0.024, OR 2.12), high initial dose of PSL (p=0.024, OR 2.69), low albumin (p=0.031, OR 3.56), and low PaCO2 (p=0.038, OR 2.67) were independent risk factors for infection. Serum samples were obtained from total of 14 patients and 13 healthy controls. Serum miR-1 levels in PM/DM-ILD patients before treatment were significantly higher than those in healthy controls (p=0.047). Also serum miR-1 levels were significantly higher in PM/DM-ILD patients with concomitant infectious diseases as compared to patients without infectious diseases (p=0.043). We further divided the PM/DM-ILD cases into two groups by the serum miR-1 level. The higher miR-1 group showed poorer effectiveness of ILD treatment (p=0.040), and lower lymphocyte count (p=0.013) as compared to the lower miR-1 group.
Conclusions Appropriate monitoring is important for PM/DM-ILD, especially in older patients with malnutrition or decreased respiratory function. miR-1 can be a new biomarker for predicting treatment response and concomitant infectious diseases during treatment for PM/DM-ILD.
Robert W. Georgantas et al, Inhibition of myogenic microRNAs 1, 133, and 206 by inflammatory cytokines links inflammation and muscle degeneration in adult inflammatory myopathies, Arthritis Rheum, 2014;66:1022–33.
Disclosure of Interest None declared
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