| Summary: | Objectives. To assess CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-) ILD in idiopathic inflammatory myopathies (IIMs). Methods. Patients with IIMs seen in our center from July 2020 to March 2021 were consecutively enrolled. ILD was detected by high-resolution CT. CCL18 and OX40L serum levels were measured by validated ELISA assays in 93 patients and 35 controls. At the 2-year follow-up, PF-ILD was evaluated according to the INBUILD criteria. Results. ILD was diagnosed in 50 (53.7%) patients. CCL18 serum levels were higher in IIMs patients vs. controls (232.9 [IQR 134.7–399.07] vs. 48.4 [29.9–147.5], <i>p</i> < 0.0001), with no difference for OX40L. IIMs-ILD patients exhibited higher levels of CCL18 than those without ILD (306.8 [190.8–520.5] vs. 162 [75.4–255.8], <i>p</i> < 0.0001). High CCL18 serum levels were independently associated with IIMs-ILD diagnosis. At follow-up, 22/50 (44%) patients developed a PF-ILD. Patients who developed PF-ILD had higher CCL18 serum levels than non-progressors (511 [307–958.7] vs. 207.1 [149.3–381.7], <i>p</i> < 0.0001). Multivariate logistic regression analysis revealed CCL18 as the only independent predictor of PF-ILD (OR 1.006 [1.002–1.011], <i>p</i> = 0.005). Conclusions. Although in a relatively small sample, our data suggest that CCL18 is a useful biomarker in IIMs-ILD, particularly in the early identification of patients at risk of developing PF-ILD.
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