Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases

Background: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA)(+) T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo. Objective: We sought to measure cytokine production by circulating skin-homing (CLA(+)) versus systemic (CLA(-)) "polar'' CD4(+)/CD8(+) ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects. Methods: Flow cytometry was used to measure levels of the cytokines IFN-gamma, IL-13, IL-9, IL-17, and IL-22 in CD4(+)/CD8(+) T cells in the blood of 19 patients with moderate-to-severe nonsegmental/generalized vitiligo, moderate-to-severe AA (n = 32), psoriasis (n = 24), or AD (n = 43) and control subjects (n = 30). Unsupervised clustering differentiated subjects into groups based on cellular frequencies. Results: Patients with Vitiligo showed the highest CLA(+)/CLA(-) T(H)1/type 1 cytotoxic T-cell polarization, with parallel T(H)2/T(H)9/T(H)17/T(H)22 level increases to levels often greater than those seen in patients with AA, AD, or psoriasis (P < .05). Total regulatory T-cell counts were lower in patients with vitiligo than in control subjects and patients with AD or psoriasis (P < .001). Vitiligo severity correlated with levels of multiple cytokines (P < .1), whereas duration was linked with IFN-gamma and IL-17 levels (P < .04). Patients and control subjects grouped into separate clusters based on blood biomarkers. Conclusions: Vitiligo is characterized by a multicytokine polarization among circulating skin-homing and systemic subsets, which differentiates it from other inflammatory/autoimmune skin diseases. Future targeted therapies should delineate the relative contribution of each cytokine axis to disease perpetuation.