ObjectiveTo evaluate sialic acid binding Ig-like lectin 1 (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 paediatric patients with the diagnosis of IIM. SIGLEC1 expression was assessed by flow cytometry and was compared with Physician Global Assessment or Childhood Myositis Assessment Scale disease activity scores. Mann Whitney U test and receiver operating characteristic 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 analysed in 14 patients within 12 months, using Wilcoxon test. SIGLEC1 was compared with interferon-stimulated gene 15/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 necrotising 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 of 0.92 (95% CI 0.83 to 1) in DM and correlated with disease activity longitudinally (aDM: standardised beta=0.54, p<0.001; jDM: standardised beta=−0.70, p<0.001). Response to treatment in DM was associated with a decreasing SIGLEC1 (p<0.01, Wilcoxon test). SIGLEC1 was found upregulated in 8 of 19 patients with AS, 2 of 9 patients with IBM but 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.
Objectives To evaluate and compare the diagnostic accuracy of SIGLEC1, a surrogate marker of type I IFN, with established biomarkers in an inception cohort of systemic lupus erythematosus (SLE). Methods SIGLEC1 was analyzed by flow cytometry in 232 patients referred to our institution with suspected SLE between October 2015 and September 2020. Results SLE was confirmed in 76 of 232 patients (32.8%) according to the 2019 EULAR/ACR classification criteria and their SIGLEC1 values were significantly higher compared with patients without SLE (p< 0.0001). A sensitivity of 98.7%, a specificity of 82.1%, a negative predictive value (NPV) of 99.2% and a positive predictive value (PPV) of 72.8% were calculated for SIGLEC1. Adjusted to the highest reported prevalence of SLE, the NPV and PPV were > 99.9% and 0.1%, respectively. Using ROC analysis and Delong testing, the area under the curve (AUC) for SIGLEC1 (AUC = 0.95) was significantly higher than for ANA (AUC = 0.88, p= 0.031), C3 (AUC = 0.83, p= 0.001) and C4 (AUC = 0.83, p= 0.002) but not for anti-dsDNA antibodies (AUC = 0.90, p= 0.163). Conclusion IFN-I pathway activation is detectable in almost all newly diagnosed SLE patients. Thus, a negative test result for SIGLEC1 is powerful to exclude SLE in suspected cases.
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