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

Lerkvaleekul, B.; Veldkamp, S.R.; Wal, M.M. van der; Schatorje, E.J.H.; Kamphuis, S.S.M.; Berg, J.M. van den; Muller, P.C.E.H.; Armbrust, W.; Vastert, S.J.; Wienke, J.; Jansen, M.H.A.; Royen-Kerkhof, A. van; Wijk, F. van

doi:doi:10.1093/rheumatology/keab601

Objective 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...Show moreObjective 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 (r(s) = 0.81, P < 0.0001) and galectin-9 (r(s) = 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.Show less

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