Type I interferon score is associated with the severity and poor prognosis in anti-MDA5 antibody-positive dermatomyositis patients

Abstract

ObjectivesTo investigate the clinical significance of the interferon (IFN) score, especially the IFN-I score, in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM).MethodsWe enrolled 262 patients with different autoimmune diseases, including idiopathic inflammatory myopathy, systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still’s disease, and Sjögren’s syndrome, as well as 58 healthy controls. Multiplex quantitative real-time polymerase chain reaction (RT-qPCR) using four TaqMan probes was used to evaluate type I IFN-stimulated genes (IFI44 and MX1), one type II IFN-stimulated gene (IRF1), and one internal control gene (HRPT1), which were used to determine the IFN-I score. The clinical features and disease activity index were compared between the high and low IFN-I score groups in 61 patients with anti-MDA5+ DM. The associations between laboratory findings and the predictive value of the baseline IFN-I score for mortality were analyzed.ResultsThe IFN score was significantly higher in patients with anti-MDA5+ DM than in healthy controls. The IFN-I score was positively correlated with the serum IFN-α concentration, ferritin concentration, and Myositis Disease Activity Assessment Visual Analogue Scale (MYOACT) score. Compared with patients with a low IFN-I score, patients with a high IFN-I score showed a higher MYOACT score, C-reactive protein concentration, aspartate transaminase concentration, ferritin concentration, plasma cell percentage, and CD3+ T-cell percentage, as well as lower lymphocyte, natural killer cell, and monocyte counts. The 3-month survival rate was significantly lower in patients with an IFN-I score of >4.9 than in those with an IFN-I score of ≤4.9 (72.9% vs. 100%, respectively; P = 0.044).ConclusionThe IFN score, especially the IFN-I score, measured by multiplex RT-qPCR is a valuable tool to monitor disease activity and predict mortality in patients with anti-MDA5+ DM.

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

“…Our proteomic data showed a substantial activation in the biological process of inflammatory response in RP-ILD patients. MDA5 + DM patients tend to have high sera inflammation status, with markedly increased serum ferritin and high type I interferon [ 25 ]. These factors are associated with the severity and poor prognosis.…”

Deciphering the crosstalk of immune dysregulation between COVID-19 and idiopathic inflammatory myopathy

“…Interferon signaling is highly represented in the muscle and skin of IIM patients, together with complement cascade activation, exerting various inflammatory effects that result in muscle fibrosis ( 50 ). In particular, interferon I signaling is increased in anti-MDA5+ dermatomyositis, which greatly correlates with disease activity and can be used to predict patient mortality ( 51 , 52 ). Therefore, we hypothesized that after COVID-19 infection, myocytes respond to external stimuli to activate complement and interferon signaling via MAPK signaling, which releases large amounts of inflammatory factors.…”

Idiopathic inflammatory myopathies: one year in review 2023

“…Many studies have been conducted on identifying specific cytokines whose over-expression may be associated with development, prognosis and clinical manifestations of IIM and most of them focused on the IFN pathway. In particular, an upregulation of IFN-I signature has been observed not only in IIM patients when compared to controls, but also in anti-MDA5 positive DM rather than in patients displaying other myositis specific autoantibody (MSA) positivity (5)(6)(7). IFN-I signature appears to be a valuable tool to predict mortality and monitor disease activity in these patients.…”

“…IFN-I signature appears to be a valuable tool to predict mortality and monitor disease activity in these patients. Moreover, IFN-I score seems to positively correlate with serum IFN-α and ferritin concentration and disease severity in anti-MDA5 DM, negatively correlating with survival rate and therefore making it a suitable prognostic biomarker (6); in this subset of patients, serum levels of IFNγ-induced protein 10 (IP-10) are higher than in controls and their levels decrease upon treatment, strictly correlating with IFN-α2 (7). An hyperexpression of IFN pathway, through the upregulation of cGAS-STING, has been assessed in muscle biopsies from IMNM and DM patients, in which cGAS-STING pathway may be involved in the development of necrosis and muscular atrophy both in IMNM and DM (8).…”