Type I interferon biomarker in idiopathic inflammatory myopathies: associations of Siglec-1 with disease activity and treatment response

Objectives: Novel biomarkers are needed to guide therapy in idiopathic inflammatory myopathies (IIM). Expression of Siglec-1, a type I interferon biomarker, was examined in adult patients with IIM in relation to disease activity and treatment response. Methods: We analyzed PBMC samples from 19 newly diagnosed adult IIM patients who participated in a phase-2 pilot study on efficacy of intravenous immunoglobulin (IVIG) monotherapy, and from 9 healthy controls. Siglec-1 expression on monocytes was measured by flow cytometry before and after treatment, and was evaluated in relation to IIM subtype, physician global activity (PhGA) scores, manual muscle strength (MMT) and the total improvement score (TIS). Results: Diagnoses included dermatomyositis (DM; n = 9), immune-mediated necrotizing myopathy (IMNM; n = 5), non-specific/overlap myositis (NSM/OM; n = 4) and antisynthetase syndrome (ASyS; n = 1). All patients showed increased Siglec-1 expression at baseline. Relative median fluorescence intensity of Siglec-1 was highest in patients with DM. After 9 weeks, follow-up samples were available for 15 patients of whom 10 patients showed a decline in Siglec-1 expression. In DM, Siglec-1 correlated with disease activity (MMT; rs =-0.603, P = 0.013 and PhGA; rs = 0.783, P < 0.001) and with the TIS (rs =-0.786, P = 0.036). Conclusion: Siglec-1 was increased in treatment-naive IIM patients and showed a decline after IVIG monotherapy. In DM, Siglec-1 expression correlated with relevant clinical measures. This underlines the dynamic role of type I IFN in IIM and the biomarker potential of Siglec-1, in particular in DM. These findings should be further validated in larger cohorts with longer follow-up.