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• W2127367165 abstract "Introduction B cells may play an important role in promoting immune activation in the rheumatoid synovium and can produce prostaglandin E2 (PGE2) when activated. In its turn, PGE2 formed by cyclooxygenase (COX) and microsomal prostaglandin E2 synthase 1 (MPGES1) contributes to the rheumatoid arthritis (RA) pathological process. Therapeutic depletion of B cells results in important improvement in controlling disease activity in rheumatoid patients. Therefore we investigated the expression of PGE2 pathway enzymes in RA B cells and evaluated the effects of B cell depleting therapy on their expression in RA tissue. Methods B cells expressing MPGES1 and COX-2 were identified by flow cytometry in in vitro stimulated and control mononuclear cells isolated from synovial fluid and peripheral blood of RA patients. Synovial biopsies were obtained from 24 RA patients before and at two consecutive time points after rituximab therapy. Expression of MPGES1, COX-1 and COX-2, as well as interleukin (IL)-1β and IL-6, known inducers of MPGES1, was quantified in immunostained biopsy sections using computerized image analysis. Results Expression of MPGES1 or COX-2 was significantly upregulated upon stimulation of B cells from blood and synovial fluid while control cells displayed no detectable enzymes. In synovial biopsy sections, the expression of MPGES1, COX-1 or COX-2 was resistant to rituximab therapy at 8 or 16 weeks after start of treatment. Furthermore expression of IL-1β in the synovial tissue remained unchanged, while IL-6 tended to decrease after therapy. Conclusions Therapy with B cell depleting agents, although efficient in achieving good clinical and radiographic response in RA patients, leaves important inflammatory pathways in the rheumatoid synovium essentially unaffected." @default.
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• W2127367165 date "2011-01-27" @default.
• W2127367165 modified "2023-10-16" @default.
• W2127367165 title "Prostaglandin E2 Synthesizing Enzymes in Rheumatoid Arthritis B Cells and the Effects of B Cell Depleting Therapy on Enzyme Expression" @default.
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• W2127367165 doi "https://doi.org/10.1371/journal.pone.0016378" @default.
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