Rheumatology Advance Access originally published online on November 3, 2006
Rheumatology 2007 46(4):657-665; doi:10.1093/rheumatology/kel346
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Distinct expression pattern of IFN-
and TNF- in juvenile idiopathic arthritis synovial tissue
Second Division of Pediatrics, ‘G. Gaslini’ Institute for Children and University of Genoa, Genoa, Italy and 1Institute of Research in Biomedicine, Bellinzona, Switzerland.
Correspondence to: M. Gattorno, MD, Second Division of Pediatrics, ‘G. Gaslini’ Institute and University of Genoa, Largo G. Gaslini 5, 16147, Genoa, Italy. E-mail: marcogattorno{at}ospedale-gaslini.ge.it
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Abstract |
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Objectives. Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-
and tumour necrosis factor (TNF)-, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN- and TNF- expression at sites of inflammation in juvenile idiopathic arthritis (JIA).
Methods. Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2+CD123+HLA-DR+CD45RA+ cells, and dendritic cells (DCs) as CD11c+CD14–/lowlin– cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN- was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-, TNF-, CD3, CD19 and CD138.
Results. IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN- release was detected from SF IPCs, and serum and SF IFN- levels were not elevated. Nonetheless, in synovial tissue IFN- producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF- producing cells were mostly found at the lining and sublining layers.
Conclusions. These data suggest that besides TNF--expressing cells, IFN--producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.
KEY WORDS: Interferon-, Plasmacytoid cells, Dendritic cells, Juvenile idiopathic arthritis
Submitted 16 December 2005;
revised version accepted 8 September 2006.
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