Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response

Lerkvaleekul B.Veldkamp S.R.Van Der Wal M.M.Schatorj E.J.H.Kamphuis S.S.M.Van Den Berg J.M.Hissink Muller P.C.E.Armbrust W.Vastert S.J.Wienke J.Jansen M.H.A.Van Royen-Kerkhof A.Van Wijk F.Mahidol University2023-06-202023-06-202022-05-01Rheumatology (United Kingdom) Vol.61 No.5 (2022) , 2144-215514620324https://repository.li.mahidol.ac.th/handle/20.500.14594/87312Objective: JDM is a rare chronic immune-mediated inflammatory disease with a predominant role for type I IFN responses. We aimed to determine the potential of Siglec-1 expression on monocytes as a novel IFN-inducible biomarker for disease activity monitoring and prediction of treatment response in patients with JDM. Methods: Siglec-1 was measured by flow cytometry on circulating monocytes of 21 newly diagnosed JDM patients before start of treatment and, for 10 of these, also during follow-up. The expression levels of five type I IFN-stimulated genes, MX1, IFI44, IFI44L, LY6E and IFIT3, were measured by RT-qPCR to determine the IFN signature and calculate an IFN score. IFN-inducible plasma proteins CXCL10 and galectin-9 were measured by multiplex immunoassay. Results: Siglec-1 and IFN score were increased in JDM patients compared with controls and correlated with clinical disease activity. Stratification of patients by Siglec-1 expression at diagnosis identified those with high Siglec-1 expression as having a higher risk of requiring treatment intensification within the first 3 months after diagnosis (55% vs 0% of patients, P = 0.01). Siglec-1 expression strongly correlated with plasma levels of previously validated biomarkers CXCL10 (rs = 0.81, P < 0.0001) and galectin-9 (rs = 0.83, P < 0.0001), and was superior to the IFN score in predicting treatment response (area under the curve 0.87 vs 0.53, P = 0.01). Conclusion: Siglec-1 on monocytes is a novel IFN-inducible biomarker in JDM that correlates with clinical disease activity and identifies patients at risk for a suboptimal treatment response. Further studies are required to validate these findings and their clinical potential.MedicineSiglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment responseArticleSCOPUS10.1093/rheumatology/keab6012-s2.0-851299985671462033234387304