Background Although several studies have reported an increased cardiovascular (CV) risk and endothelial damage in Rheumatoid Arthritis (RA) patients [1, 2], the underlying mechanisms remain unclear. The Angiogenic T cells (Tang) are a recently discovered T-cell subset with high vasculogenic profile, whose main function is supposed to be to cooperate with Endothelial Progenitor Cells (EPC) in endothelial repair . Thus, Tang disturbances could play a role in impairing endothelial repair.
Objectives The main aim of this study is to analyze the Tang and EPC populations in RA patients according to disease-specific markers and traditional CV risk factors.
Methods Tang (CD3+CD31+CD184+) and EPC (CD34+VEGFR2+CD133+) populations were quantified by flow cytometry in peripheral blood samples from 68 patients with long-standing RA (mean disease duration: 8.79 ± 6.02 years) and 18 healthy controls (HC). DAS28 score was used for measuring disease activity. IFNα serum levels were measured by Cytometric Bead Array. Clinical and immunological data and traditional CV risk factors were obtained by reviewing clinical records.
Results Both Tang and EPC were strongly depleted in RA patients (p=0.004 and p<0.0001, respectively). Tang were inversely related to traditional CV risk factors (Total cholesterol: r= -0.667, p=0.003; LDL-cholesterol: r= -0.678, p=0.002) and positively correlated with EPC (r=0.893, p<0.0001) in HC but not in RA patients. However, EPC-Tang correlation was partially recovered in those patients with low disease activity (DAS28<2.8) (r=0.447, p=0.042). In addition, Tang were negatively associated with disease activity (DAS28: r= -0.570, p<0.0001), autoantibodies positivity (ANA: p=0.003, RF: p=0.001, CCP: p=0.041) and IFNα serum levels (r= -0.337, p=0.036). Multivariate regression analysis adjusted by traditional CV risk factors revealed that only DAS28 (β[95%CI], -0.352[-2.228, -0.250], p=0.016), ANA positivity (-0.493[-0.6493,-1.745], p=0.001) and age at diagnosis (-0.287[-0.207, -0.002], p=0.045) were significant in predicting Tang frequencies in RA patients.
Interestingly, patients with previous CV events exhibited a stronger depletion (p=0.012), mainly in those ANA (+), where a mature EPC increase is also observed (p=0.021). In addition, past CV events were associated with higher IFNα levels (p=0.007).
Finally, in vitro assays confirmed the effect of IFNα on Tang population (p<0.001, n=7).
Conclusions Tang and EPC depletion could have a role in determining the increased CV risk in RA patients. Disease-specific parameters rather than traditional CV risk factors are associated with Tang in RA. Additionally, autoantibody profiles and IFNα levels could be an interesting tool to account for specific-patient CV risk.
Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D (2012); Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies; Ann Rheum Dis 71(9):1524-9.
Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA et al. (1994); The mortality of rheumatoid arthritis. Arthritis Rheum 37(4):481-94.
Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH, et al. (2007); Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation 116(15):1671-82.
Disclosure of Interest None Declared
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