Soluble SIGLEC1 as a biomarker of disease activity in idiopathic inflammatory myopathies

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OBJECTIVES: To investigate soluble circulating sialic acid-binding Ig-like lectin 1 (scSIGLEC1), a surrogate biomarker for type I IFN, as a novel biomarker for idiopathic inflammatory myopathies (IIM) disease activity. METHODS: Patients enrolled in a Canadian multicentre cohort of IIM patients with biobanked serum samples and clinical data at baseline and 1-year follow-up were included. Serum scSIGLEC1 levels at baseline were tested using a capture immunoassay and evaluated in relation to disease activity, defined using patients' Physician Global Activity (PGA) scores, Total Improvement Scores (TIS) and visual analogue scale scores for the six organ systems included in the Myositis Disease Activity Assessment Visual Analogue Scales (MYOACT): constitutional, cutaneous, skeletal, gastrointestinal, pulmonary and cardiovascular. Performance of scSIGLEC1, MYOACT and creatine kinase to assess disease activity were compared [area under the receiver operating characteristic curve (ROC AUC)]. RESULTS: A total of 87 IIM patients (67.8% female, mean age 54.4 ± 14.3 years) were included. Higher scSIGLEC1 levels differentiated between active and inactive disease on the PGA (difference 2.7 ng/ml; 95% CI 0.7-4.8). Higher scSIGLEC1 levels were found among patients with cutaneous (difference 1.7 ng/ml; 95% CI 0.1-3.4), skeletal (difference 2.0 ng/ml; 95% CI 0.1-3.9) and gastrointestinal (difference 2.2 ng/ml; 95% CI 0.5-3.9) disease activity compared with patients without disease activity in these extramuscular organs, and were associated with lower TIS scores at 1-year follow-up. scSIGLEC1 levels (ROC AUC 0.74; 95% CI 0.61-0.86) matched MYOACT performance and outperformed creatine kinase in assessing disease activity. CONCLUSION: scSIGLEC1 levels are a promising biomarker for monitoring overall IIM disease activity, as well as activity involving the cutaneous, musculoskeletal and gastrointestinal systems.

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