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. 2019 Jun;143(6):2095-2107.
doi: 10.1016/j.jaci.2018.11.031. Epub 2018 Dec 18.

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

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

Tali Czarnowicki et al. J Allergy Clin Immunol. 2019 Jun.

Abstract

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-γ, 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- TH1/type 1 cytotoxic T-cell polarization, with parallel TH2/TH9/TH17/TH22 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-γ 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.

Keywords: T(H)1; T(H)17; T(H)2; T(H)22; Vitiligo; alopecia areata; atopic dermatitis; biomarkers; endotypes; psoriasis; regulatory T.

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