Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome.

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RESEARCH PRODUCT

Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome.

Annarita Giardina Roberto Giacomelli Francesco Carubbi Angelo Ferrante Aroldo Rizzo Riccardo Alessandro Giuliana Guggino Paola Cipriani Francesco Ciccia Alessandra Cannizzaro Giovani Triolo

subject

Adult Male STAT3 Transcription Factor Sjogren Syndrome Apoptosis In Vitro Techniques Interleukin-23 Peripheral blood mononuclear cell Salivary Glands Antibodies Monoclonal Murine-Derived Rheumatology stomatognathic system Settore BIO/13 - Biologia Applicata Biopsy Humans Medicine Pharmacology (medical)Mast Cells Aged medicine.diagnostic_test business.industry Interleukins Interleukin-17 IL17 Middle Aged Mast cell In vitro Settore MED/16 - Reumatologia Sjogren's Syndrome Treatment Outcome medicine.anatomical_structure Apoptosis Antirheumatic Agents Immunology Th17 Cells Immunohistochemistry Female Rituximab Interferons Interleukin 17 business Rituximab Signal Transduction medicine.drug

description

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.

year	journal	country	edition	language
2014-01-01

10.1093/rheumatology/keu004 http://hdl.handle.net/11697/161