Francesco Ciccia1, Giuliana Guggino1, Aroldo Rizzo1, Riccardo Alessandro1, Francesco Carubbi1, AnnaRita Giardina1, Paola Cipriani1, Angelo Ferrante1, Alessandra Cannizzaro1, Roberto Giacomelli1, Giovanni Triolo2. 1. Dipartimento Biomedico di Medicina Interna e Specialistiche, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Sezione di Anatomia Patologica, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo and Dipartimento di Medicina Interna e Salute pubblica, Sezione di Reumatologia, Università di L'Aquila, L'Aquila, Italy. 2. Dipartimento Biomedico di Medicina Interna e Specialistiche, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Sezione di Anatomia Patologica, Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo and Dipartimento di Medicina Interna e Salute pubblica, Sezione di Reumatologia, Università di L'Aquila, L'Aquila, Italy. giovanni.triolo@unipa.it.
Abstract
OBJECTIVE: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS). METHODS: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments. RESULTS: IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast cells. After RTX therapy, the SG expression of IL-17, but not of IL-23p19 and p-STAT3, was significantly reduced and was accompanied by the depletion of tissue mast cells. In in vitro experiments with heterologous peripheral lymphocytes RTX significantly induced the apoptosis of isolated mast cells. Finally, mast cells isolated from peripheral blood mononuclear cells of pSS patients in vitro significantly increased Th17 lymphocytes. CONCLUSION: RTX acts on pSS patients by globally reducing the expression of IL-17 and specifically inducing a pronounced apoptotic depletion of mast cells.
OBJECTIVE: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS). METHODS: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSSpatients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments. RESULTS:IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast cells. After RTX therapy, the SG expression of IL-17, but not of IL-23p19 and p-STAT3, was significantly reduced and was accompanied by the depletion of tissue mast cells. In in vitro experiments with heterologous peripheral lymphocytes RTX significantly induced the apoptosis of isolated mast cells. Finally, mast cells isolated from peripheral blood mononuclear cells of pSSpatients in vitro significantly increased Th17 lymphocytes. CONCLUSION:RTX acts on pSSpatients by globally reducing the expression of IL-17 and specifically inducing a pronounced apoptotic depletion of mast cells.
Authors: A Alunno; F Carubbi; O Bistoni; S Caterbi; E Bartoloni; P Di Benedetto; P Cipriani; R Giacomelli; R Gerli Journal: Clin Exp Immunol Date: 2016-03-03 Impact factor: 4.330
Authors: Benjamin A Fisher; Colin C Everett; John Rout; John L O'Dwyer; Paul Emery; Costantino Pitzalis; Wan-Fai Ng; Andrew Carr; Colin T Pease; Elizabeth J Price; Nurhan Sutcliffe; Jimmy Makdissi; Anwar R Tappuni; Nagui S T Gendi; Frances C Hall; Sharon P Ruddock; Catherine Fernandez; Claire T Hulme; Kevin A Davies; Christopher John Edwards; Peter C Lanyon; Robert J Moots; Euthalia Roussou; Andrea Richards; Linda D Sharples; Michele Bombardieri; Simon J Bowman Journal: Ann Rheum Dis Date: 2017-12-23 Impact factor: 19.103