Unusual CD4+CD28− T lymphocyte subset is implicated in the pathogenesis of early atherosclerosis in patients with rheumatoid arthritis

Abstract

BackgroundRheumatoid arthritis (RA) is associated with accelerated atherosclerosis which is not fully explained by traditional risk factors. Such excess risk appears to be driven by systemic inflammation. Aim of the workAim of the work was to compare between RA patients with and without CD4+CD28− T-cell expansion regarding carotid intima-media thickness (IMT) and brachial artery flow-mediated endothelium-dependent dilatation (FMEDD), as markers of early atherosclerosis. Patients and methodsThe study was conducted on 39 female patients with no overt cardiovascular disease or risk factor and 28 age matched females as controls. Atherosclerotic changes were assessed through measurement of carotid IMT and FMEDD. CD4+CD28− T-cells were assessed by flow cytometry. ResultsThe mean age of the patients was 34.9 ± 5 years and the disease duration of 6.1 ± 2.1 years. Traditional risk factors were comparable between patients and controls. Serum homocysteine level tended to be higher in the patients (11 ± 4.21 μmol/L) compared to the control (9.91 ± 3.61 μmol/L). Patients had significantly higher carotid IMT (0.83 ± 0.24 mm vs 0.6 ± 0.15 mm, p = 0.008) and lower FMEDD (3.27 ± 1.49% vs 6.01 ± 1.79%, p = 0.002). Similarly, patients with CD4+CD28− expansion (n = 12) had significantly higher IMT (1 ± 0.23 mm) and lower FMEDD (2.25 ± 1.06%) compared to those without (n = 27) (0.76 ± 0.21 mm and 3.67 ± 1.47%); p = 0.01, p = 0.01 respectively; but not affected by receiving methotrexate or not. Laboratory investigations were comparable in patients with and without expansion. ConclusionCD4+CD28− cells may contribute to the development of premature atherosclerosis in RA patients. Further studies are recommended to evaluate the benefit of CD4+CD28− T-cell modulation on the future development of atherosclerosis in these patients.