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

Autor:	Lerkvaleekul B; Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.; Center for Translational Immunology, University Medical Center Utrecht, Utrecht., Veldkamp SR; Center for Translational Immunology, University Medical Center Utrecht, Utrecht., van der Wal MM; Center for Translational Immunology, University Medical Center Utrecht, Utrecht., Schatorjé EJH; Department of Paediatrics, Paediatric Rheumatology, Amalia Children's Hospital, Radboud University Medical Centre Nijmegen, Nijmegen., Kamphuis SSM; Paediatric Rheumatology, Sophia Children's Hospital, Erasmus University Medical Centre, Rotterdam., van den Berg JM; Department of Pediatric Immunology, Rheumatology and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam., Hissink Muller PCE; Department of Paediatric Rheumatology, Leiden University Medical Centre, Leiden., Armbrust W; Department of Pediatric Rheumatology and Immunology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen., Vastert SJ; Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., Wienke J; Center for Translational Immunology, University Medical Center Utrecht, Utrecht., Jansen MHA; Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., van Royen-Kerkhof A; Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands., van Wijk F; Center for Translational Immunology, University Medical Center Utrecht, Utrecht.
Jazyk:	angličtina
Zdroj:	Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2022 May 05; Vol. 61 (5), pp. 2144-2155.
DOI:	10.1093/rheumatology/keab601
Abstrakt:	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 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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu