T Czarnowicki1,2, H Y He1, H-C Wen1, P W Hashim1, J K Nia1, K Malik1,2,3, Y Estrada1, G W Kimmel1, M Taliercio1, J G Krueger2, E Guttman-Yassky1,2. 1. Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA. 3. SUNY Downstate College of Medicine, Brooklyn, NY, USA.
Abstract
BACKGROUND: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+ ) vs systemic (CLA- ) "polar" CD4+ and CD8+ and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe AD patients and 30 age-matched controls. RESULTS: AA patients had increased CLA+ /CLA- Th2 (P < .007), CLA+ Tc2 (P = .04), and CLA+ Th22 (P < .05) frequencies than controls. Except of CLA- Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8+ T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS: Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.
BACKGROUND: Characterizing blood profile of alopecia areata (AA) is important not only for treatment advancements, but also for possibly identifying peripheral biomarkers that will eliminate the need for scalp biopsies. We aimed to compare frequencies of skin homing (CLA+ ) vs systemic (CLA- ) "polar" CD4+ and CD8+ and activated T-cell subsets in AA vs atopic dermatitis (AD) and control blood. METHODS: Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4+ and CD8+ T cells. Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term T-cell activation. We compared peripheral blood from 32 moderate-to-severe AA adults with 43 moderate-to-severe ADpatients and 30 age-matched controls. RESULTS: AA patients had increased CLA+ /CLA- Th2 (P < .007), CLA+Tc2 (P = .04), and CLA+ Th22 (P < .05) frequencies than controls. Except of CLA- Tc1 cells (P = .03), IFN-γ levels were mostly similar between AA, AD, and controls (P > .1). ICOS and HLA-DR activation were significantly higher in AA than controls (P < .05). T regulatory cells were significantly decreased in AA patients than controls (P < .01) and were correlated with activated CD8+ T cells and with multiple cytokine subsets (P < .05). While Th2 and Tc2 clustered with disease severity, IFN-γ producing cells were linked with AA duration. CONCLUSIONS:Alopecia areata is accompanied by Th2/Tc2 activation in skin-homing and systemic subsets, correlating with disease severity, while IFN-γ is linked to disease chronicity. These data hint for a possible role of diverse T-cells subsets in disease pathogenesis and emphasize the systemic nature of AA supporting the need for systemic therapeutic strategies in severe patients.
Authors: Benjamin Ungar; Ana B Pavel; Philip M Robson; Audrey Kaufman; Alison Pruzan; Patrick Brunner; Shivani Kaushik; James G Krueger; Mark G Lebwohl; Venkatesh Mani; Zahi A Fayad; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Pract Date: 2020-07-25
Authors: Tali Czarnowicki; Helen He; Talia Canter; Joseph Han; Rachel Lefferdink; Taylor Erickson; Stephanie Rangel; Naoya Kameyama; Hyun Je Kim; Ana B Pavel; Yeriel Estrada; James G Krueger; Amy S Paller; Emma Guttman-Yassky Journal: J Allergy Clin Immunol Date: 2019-10-15 Impact factor: 10.793