The evaluation of type I interferon score in dermatomyositis, a systematic review and a meta-analysis

Dermatomyositis (DM) is a rare autoimmune systemic disorder manifesting with typical skin rashes and proximal muscle weakness. A specific clinical DM subset is characterized by the presence of the anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies. These patients are usually burdened by a severe clinical phenotype exhibiting a poor prognosis. Interestingly, a growing body of evidence has shown that (interferon) IFN signature evaluation by the assessment of type I IFN score could be a possible mechanistic biomarker for these more severe patients with DM. Thus, in this work, the difference in type I IFN score between patients with DM and healthy controls (HCs), lacking systematic synthesis of available evidence, was assessed. Moreover, the possible difference in type I IFN score between patients with DM with or without MDA5 autoantibodies was investigated. A systematic review with a meta-analysis of available literature about values of type I IFN was performed in DM and HCs. A literature search was carried out in MEDLINE, SCOPUS, and WEB OF SCIENCE databases to identify all possible relevant studies published up to May 2024 in English language. Four studies met the inclusion criteria, comparing type I IFN score between patients with DM and HCs, or between patients with or without anti-MDA5 autoantibodies. The type I IFN score was significantly higher in patients affected by DM when compared with HCs (pooled SMD = 2.27; 95 % CI: 0.71, 3.82; p = 0.004, I² = 96 %, p_{for heterogeneity} < 0.00001) and in patients with anti-MDA5 autoantibodies than those without (pooled SMD = 0.88; 95 % CI: 0.06, 1.70; p = 0.03, I² = 83 %, p_{for heterogeneity} = 0.01). In this systematic review and meta-analysis, higher values of type I IFN score were retrieved in patients with DM when compared with HCs and in patients with anti-MDA5 autoantibodies with respect to those without. Thus, the assessment of type I IFN score appears to be a valuable mechanistic biomarker to clinically profile DM patients, and particularly those with anti-MDA5 autoantibodies.