Sialic Acid-Binding Ig-Like Lectin 1: A Serological Biomarker for Pulmonary Involvement in Idiopathic Inflammatory Myopathies

Objectives Interstitial lung disease (ILD) is the most common pulmonary manifestation in idiopathic inflammatory myopathies (IIM) and a significant contributor to disease-related morbidity and mortality.[1] Sialic acid-binding Ig-like lectin 1 (SIGLEC1) is a monocyte-expressed transmembrane protein involved in the adhesion and internalization of pathogens.[2] The expression of SIGLEC1 serves as a surrogate marker for the type I interferon (IFN-I) pathway and a candidate biomarker of disease activity in IIM. [3] However, its association with pulmonary involvement has not been explored. Here, we assessed the relationship between SIGLEC1 levels and pulmonary involvement in patients with IIM. Methods Baseline sera and clinicodemographic data from IIM patients enrolled in a multicenter registry with routine bio-banked serum samples were included. SIGLEC1 levels were tested using a capture immunoassay (Aviva Systems Biology, San Diego CA). Pulmonary involvement was assessed using pulmonary disease activity defined on the Myositis Disease Activity Assessment Visual Analogue Scales Tool (score≥1.0 cm), parenchymal abnormalities on chest X-ray or high-resolution CT (including ground-glass opacities), and dyspnea due to ILD. Median serum SIGLEC1 levels (ng/mL) were compared between patients with and without these features using the Mann-Whitney U test. Results The study included 87 IIM patients (67.8% female, mean age 55.4±14.3 years) with dermatomyositis (DM, n=31), polymyositis (n=4), antisynthetase syndrome (ASyS, n=9), immune-mediated necrotizing myopathy (n=6), inclusion body myositis (n=9), and overlap myositis (OM, n=28). Median serum SIGLEC1 levels were significantly higher in IIM patients with pulmonary disease activity (5.1 vs 2.6 ng/mL; difference 2.5 ng/mL; P<0.05) and parenchymal abnormalities (5.1 vs 2.6 ng/mL; difference 2.5 ng/m; P<0.05) compared with those without these features. There were no significant differences in median serum SIGLEC1 levels between IIM patients with and without dyspnea due to ILD (4.7 vs 3.4 ng/mL; difference 1.3 ng/mL). Higher median serum SIGLEC1 levels differentiated between the presence and absence of pulmonary disease activity (5.2 vs 2.6 ng/mL; difference 2.6 ng/mL; P<0.05) when patients with DM, OM, and ASyS were grouped together. DM patients with pulmonary disease activity (5.3 vs 2.6 ng/mL; difference 2.7 ng/mL), parenchymal abnormalities (5.4 vs 3.2 ng/mL; difference 2.2 ng/mL), and dyspnea due to ILD (7.3 vs 3.8 ng/mL; difference 3.5 ng/mL) had higher median serum SIGLEC1 levels; however, these differences were not significant. Conclusion SIGLEC1 levels are a promising biomarker for assessing pulmonary involvement in patients with IIM. This finding reinforces IFN-I activity as a hallmark of IIM-ILD. Future studies are underway to evaluate SIGLEC1 levels as a biomarker of IIM-ILD. References [1.] Fathi M. Arthritis Rheum 2008;59:677-85. [2.] Yu X. Nat Commun 2014;5:4136. [3.] Biesen R. Arthritis Rheum 2008;58:1136-45.