Background The complication of interstitial lung disease (ILD) is associated with the anti-aminoacyl tRNA synthetase (aaRS) antibody or the anti-melanoma differentiation-associated gene 5 (MDA5) antibody in polymyositis (PM)/dermatomyositis (DM). Anti-MDA5 antibody is associated with clinically amyopathic DM and fatal outcome due to rapidly progressive (RP) ILD in Asia. The frequency of fatal outcome is 40-50% in RP-ILD with anti-MDA5 antibody. The pathophysiology of ILD has remained unknown sufficiently in PM/DM.
Objectives The aim of the present study was to investigate and compare the cytokine profiles in PM/DM with ILD and without ILD, to clarify the differences between anti-MDA5 antibody-positive ILD and anti-aaRS antibody-positive ILD, and to analyze the predictive factor for the prognosis of ILD in PM/DM.
Methods Fifty PM/DM patients were enrolled in this study. These patients were divided into two subsets, PM/DM without ILD and PM/DM with ILD, which included 17 and 33 patients, respectively. Moreover, 16 healthy controls (HCs) were also enrolled. Serum cytokines were measured by multiplex assay in all subjects. The levels of each cytokine were analyzed in PM/DM with ILD or without ILD. We also compared the differences between anti-MDA5 antibody-positive ILD subset and anti-aaRS antibody positive-ILD subset in PM/DM.
Results The levels of IL-6, IL-8, IL-10, IL-12, TNF-α, IFN-α, IFN-γ and IP-10 were significantly higher in the PM/DM without ILD subset than in HCs. No significant differences were found in IL-1β, IL-2, IL-4, IL-13 or IL-17 between these subsets. Moreover, the following were significantly higher in the PM/DM with ILD subset than the PM/DM without ILD subset: IL-4 (P = 0.004), IL-6 (P = 0.03), IL-8 (P = 0.03), IL-10 (P = 0.01), TNF-α (P = 0.0002) and IP-10 (P = 0.011). A multivariate analysis demonstrated that TNF-α was the cytokine most associated with ILD. Moreover, the frequencies of the complication with RP-ILD was 80% and 17% in anti- MDA5 antibody-positive ILD and anti-aaRS antibody-positive ILD, respectively. The levels of IL-8 and IFN-α were higher in anti-MDA5 subset than anti-aaRS subset. The fatal outcome due to ILD was found in the 40% of anti-MDA5 subset, although the improvement of ILD was revealed in all patients with the anti-aaRS antibody. IL-8 levels were higher in PM/DM patients with the fatal outcome due to progressive ILD than those with the improvement of ILD.
Conclusions Inflammatory cytokines, including IL-6, IL-8, TNF-α, IFN and IP-10, were involved in the pathophysiology of PM/DM. TNF-α was mainly associated with ILD in PM/DM. IL-8 and IFN-α could be closely associated with the pathophysiology of ILD in anti-MDA5 antibody-positive DM. Serum IL-8 levels might be a possible predictor for the prognosis in ILD with PM/DM.
Disclosure of Interest None Declared