Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 143, Issue 6, Pages 2095-2107Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2018.11.031
Keywords
Vitiligo; atopic dermatitis; psoriasis; alopecia areata; T(H)1; T(H)2; T(H)17; T(H)22; regulatory T; biomarkers; endotypes
Categories
Funding
- Abbvie
- Celgene
- Eli Lilly
- Janssen
- MedImmune/AstraZeneca
- Novartis
- Pfizer
- Regeneron
- Vitae
- Glenmark
- Galderma
- Asana
- Innovaderm
- Dermira
- UCB
- Amgen
- Lilly
- Merck
- Kadmon
- Boehringer
- Kyowa
- BMS
- Serono
- Biogen Idec
- Delenex
- Sanofi
- Baxter
- Paraxel
- Xenoport
- Kineta
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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.
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