Francesco Ciccia1, Aroldo Rizzo2, Giuliana Guggino1, Alberto Cavazza3, Riccardo Alessandro4, Rosario Maugeri5, Alessandra Cannizzaro2, Luigi Boiardi3, Domenico Gerardo Iacopino5, Carlo Salvarani3, Giovanni Triolo6. 1. Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo. 2. Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti 'Villa Sofia-Cervello', Palermo. 3. Unità Operativa di Reumatologia, Azienda Ospedaliera Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia. 4. Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi and. 5. Dipartimento di Emergenze, Urgenze e Neuroscienze Cliniche, Università di Palermo, Palermo, Italy. 6. Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, g.triolo@unipa.it.
Abstract
OBJECTIVE: GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. METHODS: Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression. RESULTS: IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8. CONCLUSION: Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.
OBJECTIVE: GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. METHODS: Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression. RESULTS:IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8. CONCLUSION: Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.
Authors: Ryu Watanabe; Toshihisa Maeda; Hui Zhang; Gerald J Berry; Markus Zeisbrich; Robert Brockett; Andrew E Greenstein; Lu Tian; Jörg J Goronzy; Cornelia M Weyand Journal: Circ Res Date: 2018-08-31 Impact factor: 17.367
Authors: Li-Li Pan; Juan Du; Na Gao; Hua Liao; Jin Wan; Wei-Ping Ci; Chun Yang; Tian Wang Journal: Clin Rheumatol Date: 2016-09-15 Impact factor: 2.980
Authors: Ryu Watanabe; Marc Hilhorst; Hui Zhang; Markus Zeisbrich; Gerald J Berry; Barbara B Wallis; David G Harrison; John C Giacomini; Jörg J Goronzy; Cornelia M Weyand Journal: JCI Insight Date: 2018-10-18