Blood proteomics links systemic inflammation with early atherosclerosis in moderate-to-severe atopic dermatitis

Atopic dermatitis (AD) is increasingly recognized as a systemic inflammatory disease associated with increased cardiovascular risk, yet the mechanisms linking AD to atherosclerosis and clinically relevant biomarkers of early vascular involvement remain poorly defined. We characterized the circulating proteomic profile of moderate-to-severe AD and identified biomarkers associated with subclinical atherosclerosis. In this cross-sectional study, serum samples from patients with AD (n=34), psoriasis (n=34), and healthy controls (n=20) were analyzed using proteomic panels targeting inflammatory and cardiovascular pathways. Participants underwent carotid and femoral ultrasound to detect atheromatous plaques. Compared with controls, AD showed increased circulating Th2 (CCL13, ST2, IL-13), innate (IL-6, IL-18), Th1 (IFN-γ), and Th17 (IL-17RA) markers, together with cardiovascular-related proteins including CCL19, FGF21, HGF, and P-selectin, with enrichment of atherosclerosis-related pathways. In AD, plaques were associated with higher LDL receptor, CDH5, transferrin receptor, CCL19, and CCL25, and lower IGFBP-2 levels, which also correlated with atherosclerosis burden. A composite proteomic score showed good discrimination of plaques (AUC 0.94) and outperformed traditional cardiovascular risk factors. Proteomic profiles and plaque-associated proteins differed markedly from psoriasis. These findings identify a disease-specific systemic proteomic signature in AD linked to early atherosclerosis and highlight circulating biomarkers with potential relevance for cardiovascular risk stratification.