Tali Czarnowicki1, Juana Gonzalez2, Kathleen M Bonifacio3, Avner Shemer4, Peng Xiangyu5, Norma Kunjravia3, Dana Malajian6, Judilyn Fuentes-Duculan3, Hitokazu Esaki7, Shinji Noda3, Yeriel Estrada5, Hui Xu5, Xiuzhong Zheng3, James G Krueger3, Emma Guttman-Yassky7. 1. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address: tczarnowic01@rockefeller.edu. 2. Translational Technology Core Laboratory, The Rockefeller University, New York, NY. 3. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY. 4. Department of Dermatology, Tel-Hashomer hospital, Tel Aviv, Israel. 5. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. 6. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Columbia University College of Physicians and Surgeons, New York, NY. 7. Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY; Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Abstract
BACKGROUND: Atopic dermatitis (AD) and psoriasis pathogeneses involve skin barrier impairment and immune dysregulation; however, the contribution of B-cell imbalances to these diseases has not yet been determined. OBJECTIVE: We sought to quantify B-cell populations and antibody-secreting cells in the blood of patients with AD, patients with psoriasis, and control subjects. METHODS: We studied 34 adults with moderate-to-severe AD (mean SCORAD score, 65), 24 patients with psoriasis (mean Psoriasis Area and Severity Index score, 16), and 27 healthy subjects using an 11-color flow cytometric antibody panel. IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies of plasmablasts and naive, memory, transitional, and activated B cells. RESULTS: We measured increased CD19(+)CD20(+) B-cell counts in the skin and blood of patients with AD (P < .01). Significantly higher frequencies of chronically activated CD27(+) memory and nonswitched memory B cells were observed in patients with AD (P < .05), with lower values of double-negative populations (4% for patients with AD vs. 7% for patients with psoriasis [P = .001] and 6% for control subjects [P = .02]). CD23 expression was highest in patients with AD and correlated with IgE levels (P < .01) and disease severity (r = 0.6, P = .0002). Plasmablast frequencies and IgE expression were highest in all memory subsets of patients with AD (P < .01). Finally, CD19(+)CD24(++)CD38(++) transitional and CD19(+)CD24(-)CD38(-) new memory B-cell counts were higher in patients with AD versus those in patients with psoriasis (2.8% vs. 1.4% [P = .001] and 9.2% vs. 5.7% [P = .02], respectively). CONCLUSIONS: AD is accompanied by systemic expansion of transitional and chronically activated CD27(+) memory, plasmablast, and IgE-expressing memory subsets. These data create a critical basis for the future understanding of this debilitating skin disease.
BACKGROUND:Atopic dermatitis (AD) and psoriasis pathogeneses involve skin barrier impairment and immune dysregulation; however, the contribution of B-cell imbalances to these diseases has not yet been determined. OBJECTIVE: We sought to quantify B-cell populations and antibody-secreting cells in the blood of patients with AD, patients with psoriasis, and control subjects. METHODS: We studied 34 adults with moderate-to-severe AD (mean SCORAD score, 65), 24 patients with psoriasis (mean Psoriasis Area and Severity Index score, 16), and 27 healthy subjects using an 11-color flow cytometric antibody panel. IgD/CD27 and CD24/CD38 core gating systems were used to determine frequencies of plasmablasts and naive, memory, transitional, and activated B cells. RESULTS: We measured increased CD19(+)CD20(+) B-cell counts in the skin and blood of patients with AD (P < .01). Significantly higher frequencies of chronically activated CD27(+) memory and nonswitched memory B cells were observed in patients with AD (P < .05), with lower values of double-negative populations (4% for patients with AD vs. 7% for patients with psoriasis [P = .001] and 6% for control subjects [P = .02]). CD23 expression was highest in patients with AD and correlated with IgE levels (P < .01) and disease severity (r = 0.6, P = .0002). Plasmablast frequencies and IgE expression were highest in all memory subsets of patients with AD (P < .01). Finally, CD19(+)CD24(++)CD38(++) transitional and CD19(+)CD24(-)CD38(-) new memory B-cell counts were higher in patients with AD versus those in patients with psoriasis (2.8% vs. 1.4% [P = .001] and 9.2% vs. 5.7% [P = .02], respectively). CONCLUSIONS:AD is accompanied by systemic expansion of transitional and chronically activated CD27(+) memory, plasmablast, and IgE-expressing memory subsets. These data create a critical basis for the future understanding of this debilitating skin disease.
Authors: Lam C Tsoi; Elke Rodriguez; Dora Stölzl; Ulrike Wehkamp; Jingru Sun; Sascha Gerdes; Mrinal K Sarkar; Matthias Hübenthal; Chang Zeng; Ranjitha Uppala; Xianying Xing; Frederieke Thielking; Allison C Billi; William R Swindell; Alanna Shefler; Jiahan Chen; Matthew T Patrick; Paul W Harms; J Michelle Kahlenberg; Bethany E Perez White; Emanual Maverakis; Johann E Gudjonsson; Stephan Weidinger Journal: J Allergy Clin Immunol Date: 2019-12-28 Impact factor: 10.793
Authors: Pia Rude Nielsen; Jens Ole Eriksen; Mia Dahl Sørensen; Ulrike Wehkamp; Lise M Lindahl; Michael Bzorek; Lars Iversen; Anders Woetman; Niels Ødum; Thomas Litman; Lise Mette Rahbek Gjerdrum Journal: Acta Derm Venereol Date: 2021-03-11 Impact factor: 3.875