Background/Purpose: Polymyositis (PM) / dermatomyositis (DM) are often complicated with interstitial lung disease (ILD). In PM/DM, complication with ILD is associated with anti-aminoacyl-tRNA synthetase (ARS), including Jo-1 Ab or anti-melanoma differentiation-associated gene 5 (MDA-5) Ab. Clinically amyopathic DM (CADM) patients with anti-MDA-5 Ab have frequent complications with rapidly progressive (RP) ILD, especially in East Asia, where it is classified as acute interstitial pneumonia and reflects diffuse alveolar damage upon pathological examination. In contrast, chronic ILD is frequently observed in anti-ARS Ab-associated PM/DM, which responds well to treatment with corticosteroids. The response to treatment and the mortality rate are different between anti-MDA-5 Ab-associated ILD (anti-MDA-5-ILD) and anti-ARS Ab-associated ILD (anti-ARS-ILD). The differences in pathophysiology between these two Ab-associated ILD subsets remain unknown. Therefore, we investigate various serum cytokines in patients with PM/DM with ILD, and then clarify the differences in pathophysiology between anti-MDA-5-ILD and anti-ARS-ILD.

Methods: We evaluated the serum cytokine profiles of 38 patients with PM/DM and compared the cytokine profiles of 17 patients without ILD (non-ILD subset) and 21 patients with ILD (ILD subset), as well as the anti-MDA5-ILD and anti-ARS-ILD subsets. The levels of serum cytokines, including IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, TNF-α, IFN-α, IFN-γ, and interferon γ-inducible 10-kd (IP-10), were measured by multiplex assay. In addition, serum was obtained from 15 healthy controls (HCs).

Results: Serum IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-α, IFN-γ and IP-10 were significantly higher in PM/DM patients than HCs. Moreover, the levels of IL-4, IL-6, IL-8, IL-10, TNF-α and IP-10 were significantly higher in the ILD subset than the non-ILD subset. By multivariate analysis, TNF-α was the most significant cytokine (P = 0.0006, odds ratio 1.4, CI 1.1-2.2) associated with PM/DM with ILD. Regarding to the comparison between 10 patients with anti-MDA-5-ILD and 11 patients with anti-ARS-ILD, IL-8 level was significantly higher in the anti-MDA-5-ILD subset than the anti-ARS-ILD subset. Lower levels of IL-4 and higher levels of IL-10 and IFN-α were found in the anti-MDA-5-ILD subset than those in the anti-ARS-ILD subset. By multivariate analysis, IL-8 was the most cytokine that was most significantly associated with anti-MDA-5-ILD (P = 0.0006, odds ratio 1.5, confidence interval [CI] 1.1-3.0). In addition, the IL-4 level was inversely associated with anti-MDA-5-ILD (P = 0.01, odds ratio 0.8, CI 0.6-0.98). Moreover, the ratio of serum IL-4 to IFN-γ, which may reflect a balance between T helper 1 (T_H1) and 2 (T_H2) cells, was lower in anti-MDA-5-ILD (median value 0.16) than in anti-ARS-ILD (median value 2.0).

Conclusion: TNF-α is an especially important in contributing to ILD in PM/DM. Serum IL-8 levels and the balance between IL-4 and IFN-γ may contribute to the differences in pathophysiology between chronic ILD (anti-ARS-ILD) and RP-ILD (anti-MDA-5-ILD).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cytokine-profiles-in-polymyositis-and-dermatomyositis-complicated-with-anti-melanoma-differentiation-associated-gene-5-antibody-associated-interstitial-lung-disease-or-anti-aminoacyl-trna-synthetase-a/