Background Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease and accelerated progression of atherosclerosis. Altered populations of T-lymphocytes are associated with atherosclerosis, and chronic infection with cytomegalovirus (CMV) affects the T-cell-population.
Objectives To study the association between subsets of T-lymphocytes, subclinical atherosclerosis assessed by intima-media thickness (IMT) and antibodies against CMV in patients with RA.
Methods Patients with new-onset RA (n=71), aged ≤60 years at diagnosis, were consecutively included in a study of development of atherosclerosis. Ultrasound measurement of IMT of a. carotis communis was undertaken at inclusion (T0), after five years (T5) and after 11 years (T11) (n=54). At T11, flow-cytometry was undertaken to investigate subsets of T-lymphocytes (CD45+CD3+), where CD4, CD8, CD28, CD56 and CX3CR1 was studied. CX3CR1 is the ligand of fractalkine, an adhesion molecule expressed on activated endothelial cells to attract leukocytes. Serological analysis for CMV was undertaken from samples collected at T0, T5 and T11.
Results The percentage of CD8+T-lymphocytes lacking the co-stimulatory molecule CD28 (CD8+CD28-) was significantly (standardized beta coefficient 0.39, p-value 0.01) associated with IMT at T11 in a linear regression model including T0 variables smoking, systolic blood pressure and cholesterol. No association with IMT was seen for CD4+CD28- T-lymphocytes. CX3CR1 was expressed in 71% of CD8+CD28- T-lymphocytes, compared with 8.2% of CD8+CD28+. The prevalence of immunoglobulin G seropositivity for CMV was 47/70 (67%), 42/66 (57%) and 34/56 (52%) at T0, T5 and T11 respectively. Patients with constantly positive CMV serologies (T0, T5 and T11) had a significantly higher percentage of CD8+CD28- and CD4+CD28- T-lymphocytes. Also the proportion of cells expressing CX3CR1 was in both CD4+ and CD8+ T-lymphocytes associated with constantly positive serologies for CMV.
Conclusions Subclinical atherosclerosis in patients with RA was associated with CD8+CD28- T-lymphocytes in a regression model adjusted for traditional cardiovascular risk factors. Positive serologies for CMV were associated with an increased proportion of CD8+CD28- T-lymphocytes and T-lymphocytes expressing CX3CR1.
Disclosure of Interest B. Wahlin: None declared, A. Fasth Employee of: Novartis Sweden AB, K. Karp: None declared, K. Lejon: None declared, A. Södergren: None declared, S. Wållberg-Jonsson: None declared