TH1/TH17 cell recognition of desmoglein 3 and bullous pemphigoid antigen 180 in patients with lichen planus Thomas Schmidt, PhD, Farzan Solimani, MD,

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Presentation transcript:

TH1/TH17 cell recognition of desmoglein 3 and bullous pemphigoid antigen 180 in patients with lichen planus Thomas Schmidt, PhD, Farzan Solimani, MD, Robert Pollmann, MSc, Ronja Stein, DMD, Ansgar Schmidt, PhD, Inna Stulberg, Katja Kühn, MD, Rüdiger Eming, MD, Verena Eubel, MD, Peter Kind, MD, Nicole Arweiler, MD, Cassian Sitaru, MD, Michael Hertl, MD Journal of Allergy and Clinical Immunology Volume 142, Issue 2, Pages 669-672.e7 (August 2018) DOI: 10.1016/j.jaci.2018.02.044 Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Peripheral blood TH1/TH17 cell recognition of Dsg3 and BP180 in patients with LP. A, Clinical phenotype of LP of the oral mucosa, PV, LP of the skin, LPP, and BP. B-D, ELISpot analysis of IFN-γ–, IL-17A–, and IL-5–secreting T cells from patients with LP on stimulation with Dsg3 and Dsg1, respectively. HCs, n = 18; LP Skin, n = 13; LP Mucosa, n = 18-24; LP Total, n = 31-37. The line represents the median. *P < .05 compared with HCs, as determined by using the Mann-Whitney U or Student t test. E, IFN-γ+ and IL-5+ spot counts of patients with PV and those with LP on stimulation with Dsg3. *P < .05 and **P < .01 compared with patients with PV. F, ratio of IFN-γ+/IL-5+ spot counts of patients with LP on stimulation with Dsg3. Values are based on Fig 1, E. **P < .01 compared with patients with PV. G-I, Spot counts of IFN-γ–, IL-17A–, and IL-5–secreting T cells from patients with LP responsive to BP180-NH2 and BP180-COOH, respectively. BP180-NH2: HCs, n = 18; LP Skin, n = 13; LP Mucosa, n = 30-31; LP Total, n = 43-44. BP180-COOH: HCs, n = 18; LP Skin, n = 13; LP Mucosa, n = 15; LP Total, n = 28. The line represents the median. *P < .05 and **P < .01 compared with HCs, as determined by using the Mann-Whitney U or Student t test. J, IFN-γ+ and IL-5+ spot counts of patients with BP and those with LP on stimulation with BP180-NH2. *P < .05 compared with patients with BP. K, Ratio of IFN-γ+/IL-5+ spot counts of patients with LP on stimulation with BP180-NH2. Values are based on Fig 1, J. *P < .05 compared with patients with BP. Muc., Mucosal or mucocutaneous lesions; Skin, skin lesions only; Total, all studied patients with LP. Journal of Allergy and Clinical Immunology 2018 142, 669-672.e7DOI: (10.1016/j.jaci.2018.02.044) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 TH1/TH17 cell–dominated infiltrate of skin lesions of patients with LP. A, Representative images of immunohistologic T-cell subset analyses (CD3, CD4, and CD8: ×100 magnification; CD3/T-bet, CD4/GATA-3, and IL-17A: ×200 magnification) in skin lesions of patients with LP and those with BP. Representative image of IL-17A+ cells along the dermal-epidermal BMZ (interrupted line) and upper dermis in patients with LP and those with BP are shown. B, Numbers of IL-17A+ cells along the BMZ and upper dermis (Skin, n = 12; Mucosa, n = 15; BP, n = 12). **P < .01, Mann-Whitney U or Student t test. C, Quantification of T-cell subsets as a percentage of total infiltrating cells in skin lesions of patients with LP (n = 12), patients with BP (n = 12) and patients with PV (n = 7). D, Numbers of CD3+/T-bet+ and CD4+/GATA-3+ T cells in skin lesions of patients with LP (n = 10), patients with BP (n = 10), and patients with PV (n = 5) as a percentage of CD3+ or CD4+ T cells, respectively. *P < .05, **P < .01, and ***P < .001, as determined by using the Mann-Whitney U or Student t test. E, Ratio of T-bet+/GATA-3+ T cells in skin lesions from patients with LP, patients with BP, and patients with PV. *P < .05 compared with patients with PV and **P < .01 compared with patients with BP. F, Clinical phenotype of 3 patients with LPP (P1-P3) with positive direct immunofluorescence (C3 deposits along BMZ). G, Immunohistochemistry of representative skin lesion (P3): *subepidermal blister, **band-like subepidermal CD3+T-bet+ dermal T-cell infiltrate, and ***perivascular CD4+GATA-3+ T-cell infiltrate. H, Spot counts and ratios of CD3+/T-bet+ and CD4+/GATA-3+ T cells in skin lesions of patients with LPP as a percentage of CD3+ and CD4+ T cells, respectively. I, Spot counts and ratios of IFN-γ– and IL-5–secreting peripheral blood T cells of patients with LPP on stimulation with BP180-NH2. Journal of Allergy and Clinical Immunology 2018 142, 669-672.e7DOI: (10.1016/j.jaci.2018.02.044) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Expression of skin-homing factor CCR4 on peripheral blood T-cell subsets and chemokine plasma levels in patients with LP. A, CXCL8 plasma levels (in picograms per milliliter; dashed line indicated ELISA cutoff, 15.6 pg/mL), CXCL10 plasma levels (picograms per milliliter; dashed line indicates ELISA cutoff, 15.6 pg/mL), and CCL5/RANTES plasma levels (in nanograms per milliliter; ELISA cutoff, 7.8 pg/mL). HC subjects, n = 18; LP Skin, n = 13; LP Mucosa, n = 30; LP Total, n = 43. B, Representative dot blots of surface expression of skin-homing factor CCR4 of CD3+CD8+ and CD3+CD8− cell subsets and CCR4+ T lymphocytes as a percentage of the CD3+CD8+ and CD3+CD8− T-cell populations, respectively. HC subjects, n = 14; LP Skin, n = 5; LP Mucosa, n = 21; LP Total, n = 26. C, Peripheral CD8+ and CD4+ T lymphocytes as percentages of total CD3+ T cells. HC subjects, n = 20; LP Skin, n = 12; LP Mucosa, n = 26; LP Total, n = 38. Skin was defined as skin lesions only, Mucosa as mucosal or mucocutaneous lesions, and Total as all studied LP patients. The line represents the median. *P < .05, **P < .01, and ***P < .001 compared with HC subjects, as determined by using the Mann-Whitney U or Student t test. Journal of Allergy and Clinical Immunology 2018 142, 669-672.e7DOI: (10.1016/j.jaci.2018.02.044) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Analysis of regulatory T cells in skin lesions of patients with LP and those with BP. A, Representative image of FoxP3+ cells in the upper dermis and dermal-epidermal BMZ (interrupted line) in patients with LP and those with BP, showing a diffuse distribution of Foxp3+ regulatory T cells. B, Number of FoxP3+ cells along the BMZ and upper dermis (patients with LP, n = 8; patients with BP, n = 10). No statistically significant difference in distribution of regulatory T cells was observed between the BMZ and upper dermis, as determined by using the Mann-Whitney U test. Journal of Allergy and Clinical Immunology 2018 142, 669-672.e7DOI: (10.1016/j.jaci.2018.02.044) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Analysis of T-lymphocyte subsets in skin lesions of patients with LP, patients with BP, and patients with PV. A, Enumeration of T cells was based on use of a microscope (Axiostar, Zeiss) in combination with CellˆD (Soft Imaging System) and ImageJ software. For counting of specifically stained T cells, images of skin lesions at ×100 or ×200 magnification were taken. After generating a grid (ImageJ software; area per point, 50,000 square pixels), all infiltrating and specifically stained cells were counted in 2 defined squares (S1/S2; 4 squares for ×200 magnification) adjacent to the dermal-epidermal BMZ (ImageJ software, cell counter), and the proportion of all infiltrating cells to specifically stained T cells was determined. B, For localization analysis of IL-17A+ and FoxP3+ T cells, images were taken at ×200 magnification and after grid formation (ImageJ software; area per point, 50,000 square pixels). All infiltrating and specifically stained cells were counted in 4 squares adjacent to the BMZ (B1-B4) and 4 squares in the adjacent upper dermal region (D1-D4; ImageJ software, cell counter). The proportion of specifically stained T cells of all infiltrating cells was determined, as were the numbers of IL-17A+ T cell along the BMZ and upper dermis. Journal of Allergy and Clinical Immunology 2018 142, 669-672.e7DOI: (10.1016/j.jaci.2018.02.044) Copyright © 2018 American Academy of Allergy, Asthma & Immunology Terms and Conditions