Background Underlying mechanisms behind increased cardiovascular (CV) risk in Rheumatoid Arthritis (RA) remain unknown, but chronic inflammation and disease activity are supposed to play an important role. The Angiogenic T cells (Tang) are a recently described T-cell subset with potential function in endothelial repair, similar to Endothelial Progenitor Cells (EPC). Thus, Tang disturbances could play a role in impairing endothelial repair. The main aim of this study was to analyse the Tang and EPC populations in RA patients according to disease-specific markers and traditional CV risk factors. Since microparticles have emerged as a new tool to study endothelial damage and CV risk, we also have studied Tang-derived MP in RA.
Material and Methods Tang (CD3+ CD31+ CD184+) and EPC (CD34+ VEGFR2+ CD133+) populations were quantified by flow cytometry in peripheral blood samples from 103 RA and 18 healthy controls (HC). DAS28 score was used for measuring disease activity. IFNa serum levels were measured by Cytometric Bead Array. Clinical and immunological data and traditional CV risk factors were obtained by reviewing clinical records. Tang-derived microparticles (Tang-MP) were analysed from platelet-poor plasma samples based on their CD3 and CD31 expression.
Results Both Tang and EPC were strongly depleted in RA patients (p < 0.001 and p < 0.0001). Tang were positively correlated with EPC and negatively with traditional CV risk factors in HC but not in patients. In RA, reduced Tang numbers were associated with disease activity (r = -0.519, p < 0.0001), autoantibodies positivity (ANA: p = 0.003, RF: p = 0.006, aCCP: p = 0.003) and IFNa serum levels (r = -0.321, p = 0.001), regardless of disease duration. EPC-Tang correlation was partially recovered in those patients under remission (DAS28 <2.6; r = 0.474, p = 0.013). Multivariate regression analysis adjusted by traditional CV risk factors confirmed that only disease-specific factors and smoking were significant predictors of Tang frequency in RA. Interestingly, patients with previous CV events exhibited strongly reduced Tang numbers (p = 0.004) and higher IFNa levels (p = 0.019). Additionally, Tang-MP were increased in patients (p = 0.003) and positively correlated with DAS28 (r = 0.293, p = 0.006). In contrast, in HC a negative correlation between Tang frequency and Tang-MP was found (r = -0.502, p = 0.034). Methotrexate treatment seem to increase Tang frecuency (p = 0.020) as well as to reduce Tang-MP counts (p = 0.048).
Conclusions Tang and EPC depletion could have a role in determining the increased CV risk in RA. Disease-specific factors, autoantibodies and IFNa serum levels could account for this effect. Probably, disease-activity factors are injuring Tang subpopulation, leading to higher numbers of Tang-MP and thus, leading to a Tang failure.