SIGLEC1 enables straightforward assessment of type I interferon activity in inflammatory myopathies
SIGLEC1 enables straightforward assessment of type I interferon activity in inflammatory myopathies
Abstract ObjectiveTo evaluate SIGLEC1 expression on monocytes by flow cytometry as a type I interferon biomarker in idiopathic inflammatory myopathies (IIM). MethodsWe performed a retrospective analysis of adult and pediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment (PGA) or Childhood Myositis Assessment Scale (CMAS) disease activity scores. Mann Whitney-U test and receiver operating characteristic (ROC) curves were used for cross-sectional data analysis (n=96), two-level mixed-effects linear regression model for longitudinal analyses (n=26, 110 visits). Response to treatment was analyzed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared to ISG15/MxA status by immunohistochemical staining of muscle biopsies (n=17). Results96 patients with adult (a) and juvenile (j) dermatomyositis (DM, n=38), antisynthetase syndrome (AS, n=19), immune-mediated necrotizing myopathy (IMNM, n=8), inclusion body myositis (IBM, n=9), and overlap myositis (n=22) were included. SIGLEC1 distinguished significantly between active and inactive disease with an area under the curve (AUC) of 0.92 (95% CI: 0.83–1) in DM and correlated with disease activity longitudinally (aDM: standardized beta=0.54, p<0.001; jDM: standardized beta=-0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). A positive ISG15/MxA stain was highly associated with a SIGLEC1 upregulation. SIGLEC1 was found upregulated in AS (42.1%) and IBM (22,2%) and not in IMNM. ConclusionSIGLEC1 is a candidate biomarker to assess type I interferon activity in IIM and proved useful for monitoring disease activity and response to treatment in juvenile and adult DM. Key messagesWhat is already known about this subject?There is an unmet need for routine clinical biomarkers to assess type I interferon activity in rheumatic musculoskeletal diseasesSIGLEC1 is part of the type I interferon signature and transcripts were found to be upregulated in various autoimmune diseases such as systemic lupus erythematosus (SLE), Sjoegren syndrome and dermatomyositis.SIGLEC1 is expressed on the surface of monocytes and thus is easily assessable by flow cytometry, which enables straightforward monitoring of type I interferon activityWhat does this study add?An activation of the type I interferon system in IIM can be identified by flow cytometry analysing SIGLEC1 expression. SIGLEC1 correlated to disease activity and improvement under therapy in juvenile and adult dermatomyositis.How might this impact on clinical practice or future developments?SIGLEC1 expression is a suitable biomarker for monitoring type I interferon activation in rheumatic musculoskeletal diseases, which has clinical implications for patient stratification and treatment decision making especially in the context of interferon inhibitory therapies.
Krusche Martin、Stenzel Werner、Schneider Udo、Meisel Christian、von Stuckrad Sae Lim、Unterwalder Nadine、Buttgereit Thomas、Zorn-Pauly Lydia、Uruha Akinori、Rose Thomas、Burmester Gerd R.、Hiepe Falk、Kallinich Tilman、Biesen Robert、Graf Manuel、Klotsche Jens
Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of NeuropathologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyLabor Berlin ¨C Charit¨| Vivantes GmbH, Department of ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Pediatric Pneumology, Immunology and Critical Care Medicine and SPZ (Center for Chronically Sick Children)Labor Berlin ¨C Charit¨| Vivantes GmbH, Department of ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Dermatology and Allergy, Dermatological Allergology, Allergie-Centrum-Charit¨|Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Neuropathology||Tokyo Metropolitan Neurological Hospital, Department of NeurologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Pediatric Pneumology, Immunology and Critical Care Medicine and SPZ (Center for Chronically Sick Children)||German Rheumatism Research Center Berlin ¨C a Leibniz Institute (DRFZ)Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyCharit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin and Humboldt-Universit?t zu Berlin, Department of Rheumatology and Clinical ImmunologyGerman Rheumatism Research Center Berlin ¨C a Leibniz Institute (DRFZ)
医学研究方法基础医学内科学
Krusche Martin,Stenzel Werner,Schneider Udo,Meisel Christian,von Stuckrad Sae Lim,Unterwalder Nadine,Buttgereit Thomas,Zorn-Pauly Lydia,Uruha Akinori,Rose Thomas,Burmester Gerd R.,Hiepe Falk,Kallinich Tilman,Biesen Robert,Graf Manuel,Klotsche Jens.SIGLEC1 enables straightforward assessment of type I interferon activity in inflammatory myopathies[EB/OL].(2025-03-28)[2025-05-29].https://www.medrxiv.org/content/10.1101/2021.09.13.21263325.点此复制
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