Surface expression of fractalkine receptor (CX3CR1) on CD4+/CD28-. T cells in RA patients and correlation with atherosclerotic damage

Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes–macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the expression of fractalkine receptor (CX3CR1) on CD4+/CD28− T cells, a subset involved in atherosclerotic infiltration; the correlation between this subset and validated markers of early atherosclerosis. CD4+ T cells were isolated by immunomagnetics beads in 50 early RA patients and 26 healthy controls (HC). After isolation, CD4+/CD28−/CX3CR1+ T lymphocytes were assessed by FACS analysis. Endothelial dysfunction was evaluated by both carotid intima-media thickness (IMT) and flow-mediated vasodilation (FMV).We observed: a higher expansion of CD4+/CD28− subset in RA patients when compared to HC (7.7%, 5.15–9.7 vs. 0.7%, 0.2–1.5, P <0.01; respectively); this expansion directly correlated with increased IMT (0.91 mm, 0.5–1.3 vs. 0.7 mm, 0.2–1, P < 0.01; RA vs. C, respectively) and inversely correlated with FMV (3.5%, 1.7–7 vs. 9%, 3.5–11, P < 0.01; RA vs. C, respectively); the large majority of CD4+/CD28−, in RA, coexpressed CX3CR1 (93%, 67–99 vs. 30%, 10–48, P < 0.01; RA vs. C, respectively); this expansion significantly correlated with both the parameters of premature vascular damage and DAS 28. Our data suggest that CX3CL1/CX3CR1 axis might play a role in the induction and development of the endothelial dysfunction during RA.