698 Validation of CXCL9 as a biomarker in morphea

Abstract

Morphea, also known as localized scleroderma, is a skin condition that has an initial presentation of inflammation followed by sclerosis. Clinical disease state (active versus inactive) is difficult to ascertain in morphea using clinical examination alone. To date, no biomarkers indicative of disease activity and/or severity have been validated in morphea. Biomarkers are needed to help guide clinical assessment of patients to determine 1) disease state, 2) subclinically active disease, and 3) early detection of recurrence of activity. Based on our preliminary studies, we hypothesize that interferon-gamma regulated chemokines, particularly CXCL9, may serve as useful biomarkers of morphea disease state. We analyzed baseline sera samples from 387 patients with morphea using enzyme-linked immunoassays to quantify CXCL9 levels. Analysis revealed morphea patients had elevated CXCL9 levels (median 81.6pg/mL, IQR 45.8-177.0) when compared to 26 age, race, and gender-matched controls (59.7pg/mL, IQR 44.1-79.8) (p=0.05). Importantly, CXCL9 levels were more highly elevated in those with active morphea (defined by a mLoSSI score >3) compared to inactive morphea, where median values were similar to that of controls (median 118.1 vs 59.7, IQR 53.8-278.3 vs 44.1-79.8) (p=0.003). CXCL9 also demonstrated correlation with clinical outcome measures indicative of an active disease state (activity component of the validated LoSCAT) (r=0.36, p<0.0001). Longitudinal analysis of 58 patients followed over a mean of 5 years with a median of 3 follow-up visits corroborated these results and also identified a correlation between elevated CXCL9 levels with increased age and greater functional involvement. Taken together, this study further validates CXCL9 as a biomarker for activity in morphea. Furthermore, it may be useful in monitoring for disease recurrence as elevations may occur prior to clinically evident activity. Consideration should be made to incorporate this measure as a supplement to clinical assessment.