Background: Whereas the pathogenic role of Th17 cells in animal models of inflammatory arthritis is unchallenged, their relation with disease activity in arthritis patients and with the different types of arthritis is still controversial. Objectives: To define the presence of Th17 and Th1 in synovial fluid (SF) and peripheral blood (PB) of patients with different inflammatory arthritides and their relation with disease activity. We also investigated the cytokine production in relation to TCR-zeta chain and ZAP-70 levels. Methods: PB and SF mononuclear cells from 16 RA, 9 SpA, and 3 microcrystal arthritis patients were analyzed after stimulation with PMA plus ionomycin or anti-CD3/CD28/CD2. Th17 and Th1 percentages and TCR-zeta and ZAP-70 mean fluorescence intensity were assessed by flow cytometry. Results: Th17 were significantly higher in SF than in PB. SF Th17 were not significantly different between RA and SpA, but they were significantly higher in microcrystal arthritis compared to RA and SpA patients and in seronegative compared to seropositive RA patients. Irrespectively from the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (CRP, fibrinogen, ESR) inflammation markers, and, in RA patients, worse clinical disease activity indices (TJC, RAI, DAS44, DAS-CRP, HAQ) were associated to higher SF Th17 percentages (Figure 1). SF Th1 percentages directly correlated with systemic inflammation (CRP) and disease activity indices (SJC) in SpA, but an inverse correlation was found in RA patients (SJC, RAI, DAS44). TCR-zetadim lymphocytes were found to produce the highest amounts of IL-17 and IFN-γ in SF at single cell level. Conclusion: These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. TCR-zetadim lymphocytes can contribute to articular inflammation by releasing high amounts of cytokines, including IL-17.

Synovial fluid-derived TH17 cells correlate with disease activity in arthritis, irrespective of diagnosis

Gremese E;
2010-01-01

Abstract

Background: Whereas the pathogenic role of Th17 cells in animal models of inflammatory arthritis is unchallenged, their relation with disease activity in arthritis patients and with the different types of arthritis is still controversial. Objectives: To define the presence of Th17 and Th1 in synovial fluid (SF) and peripheral blood (PB) of patients with different inflammatory arthritides and their relation with disease activity. We also investigated the cytokine production in relation to TCR-zeta chain and ZAP-70 levels. Methods: PB and SF mononuclear cells from 16 RA, 9 SpA, and 3 microcrystal arthritis patients were analyzed after stimulation with PMA plus ionomycin or anti-CD3/CD28/CD2. Th17 and Th1 percentages and TCR-zeta and ZAP-70 mean fluorescence intensity were assessed by flow cytometry. Results: Th17 were significantly higher in SF than in PB. SF Th17 were not significantly different between RA and SpA, but they were significantly higher in microcrystal arthritis compared to RA and SpA patients and in seronegative compared to seropositive RA patients. Irrespectively from the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (CRP, fibrinogen, ESR) inflammation markers, and, in RA patients, worse clinical disease activity indices (TJC, RAI, DAS44, DAS-CRP, HAQ) were associated to higher SF Th17 percentages (Figure 1). SF Th1 percentages directly correlated with systemic inflammation (CRP) and disease activity indices (SJC) in SpA, but an inverse correlation was found in RA patients (SJC, RAI, DAS44). TCR-zetadim lymphocytes were found to produce the highest amounts of IL-17 and IFN-γ in SF at single cell level. Conclusion: These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. TCR-zetadim lymphocytes can contribute to articular inflammation by releasing high amounts of cytokines, including IL-17.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11699/85818
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