386 Biomarkers of alopecia areata in blood reveal systemic immune and cardiovascular abnormalities

Abstract

Alopecia areata (AA) is a common nonscarring hair loss disorder with a lifetime risk of 2%. Although AA is characterized by Th1/IFN-skewing, with additional Th2 and IL-23 activation in scalp tissues, little is known about its systemic profile in blood. To evaluate the blood proteomic signature of AA and determine serum biomarkers associated with increased disease severity, we assessed ∼350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in 35 moderate-to-severe AA patients (>30% scalp involvement, mean age=43.17 years; mean SALT=74.98), in comparison with age-matched healthy individuals, and as a point of reference also to moderate-to-severe psoriasis (n=19, mean PASI=20.43), and atopic dermatitis/AD patients (n=36, mean SCORAD=61.35). 74 proteins were significantly differentially expressed between AA and controls (FCH>1.3, FDR<.05) including innate immunity (IL-6, IL-8), Th1 (CXCL9/CXCL10/CXCL11/IFNG), Th2 (CCL13/CCL17/CCL7), and Th17 markers (CCL20/PI3/S100A12). 86 biomarkers were correlated with clinical severity in AA patients (P<.05) including Th1 (CCL3), Th2 (CCL11/CCL13), innate (IL8) and Th17 markers (S100A12). Many cardiovascular/atherosclerosis-related proteins were significantly higher in AA compared to controls, and also correlated with severity, including SELP, SRC, AXIN1, MPO, IL18, and OSM (P<.05). Pathway analysis showed significant increases in cardiovascular/atherosclerosis, and immune pathways compared to controls (FCH>4.0, FDR<.001), which also correlated with clinical severity (P<.05). This study defined the abnormalities of moderate-to-severe AA and associated circulatory biomarkers. It shows that AA is a systemic disease with immune, cardiovascular and atherosclerosis dysregulation, highlighting the need for systemic treatment approaches.