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Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.
J Allergy Clin Immunol. 2019 06; 143(6):2095-2107.JA

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.

Authors+Show Affiliations

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: emma.guttman@mountsinai.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30576756

Citation

Czarnowicki, Tali, et al. "Blood Endotyping Distinguishes the Profile of Vitiligo From That of Other Inflammatory and Autoimmune Skin Diseases." The Journal of Allergy and Clinical Immunology, vol. 143, no. 6, 2019, pp. 2095-2107.
Czarnowicki T, He H, Leonard A, et al. Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases. J Allergy Clin Immunol. 2019;143(6):2095-2107.
Czarnowicki, T., He, H., Leonard, A., Kim, H. J., Kameyama, N., Pavel, A. B., Li, R., Estrada, Y., Wen, H. C., Kimmel, G. W., Kim, H. J., Chima, M., Lebwohl, M., Krueger, J. G., & Guttman-Yassky, E. (2019). Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases. The Journal of Allergy and Clinical Immunology, 143(6), 2095-2107. https://doi.org/10.1016/j.jaci.2018.11.031
Czarnowicki T, et al. Blood Endotyping Distinguishes the Profile of Vitiligo From That of Other Inflammatory and Autoimmune Skin Diseases. J Allergy Clin Immunol. 2019;143(6):2095-2107. PubMed PMID: 30576756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases. AU - Czarnowicki,Tali, AU - He,Helen, AU - Leonard,Alexandra, AU - Kim,Hyun Je, AU - Kameyama,Naoya, AU - Pavel,Ana B, AU - Li,Randall, AU - Estrada,Yeriel, AU - Wen,Huei-Chi, AU - Kimmel,Grace W, AU - Kim,Hee J, AU - Chima,Margot, AU - Lebwohl,Mark, AU - Krueger,James G, AU - Guttman-Yassky,Emma, Y1 - 2018/12/18/ PY - 2018/08/05/received PY - 2018/11/02/revised PY - 2018/11/09/accepted PY - 2018/12/24/pubmed PY - 2020/5/6/medline PY - 2018/12/22/entrez KW - T(H)1 KW - T(H)17 KW - T(H)2 KW - T(H)22 KW - Vitiligo KW - alopecia areata KW - atopic dermatitis KW - biomarkers KW - endotypes KW - psoriasis KW - regulatory T SP - 2095 EP - 2107 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 143 IS - 6 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/30576756/Blood_endotyping_distinguishes_the_profile_of_vitiligo_from_that_of_other_inflammatory_and_autoimmune_skin_diseases_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(18)32729-5 DB - PRIME DP - Unbound Medicine ER -