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Atherosclerosis in rheumatoid arthritis: associations between anti-cytomegalovirus IgG antibodies, CD4+CD28null T-cells, CD8+CD28null T-cells and intima-media thickness
B. Wahlin1, A.E. Fasth2, K. Karp3, K. Lejon4, V. Malmström5, A. Rahbar6, S. Wållberg-Jonsson7, A. Södergren8
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Sweden. bengt.wahlin@umu.se
- Rheumatology Division, Department of Medicine at Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
- Department of Surgical and Perioperative Sciences/Clinical physiology, Umeå University, Sweden.
- Department of Clinical Microbiology, Infection and Immunology, Umeå University, Sweden.
- Rheumatology Division, Department of Medicine at Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
- Division of Microbial Pathogens, BioClinicum, Department of Medicine at Solna, Karolinska Universtity Hospital, Karolinska Institutet, Stockholm, Sweden.
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Sweden.
- Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, and Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Sweden.
CER13194
2021 Vol.39, N°3
PI 0578, PF 0586
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PMID: 32896254 [PubMed]
Received: 10/02/2020
Accepted : 01/06/2020
In Press: 03/09/2020
Published: 21/05/2021
Abstract
OBJECTIVES:
Patients with rheumatoid arthritis (RA) have an accelerated progression of atherosclerosis. The aims of this study were to study the associations between subsets of T-cells, subclinical atherosclerosis assessed by intima-media thickness (IMT) and serological status for CMV in patients with RA.
METHODS:
Patients with new-onset RA (n=79), aged ≤60 years at diagnosis, were included in a prospective study of atherosclerosis. Controls matched for age and sex were also included (n=44). Ultrasound measurement of IMT in the common carotid artery was undertaken at inclusion (T0), after 1.5 years (T1.5) and after 11 years (T11). At T11, flow-cytometry analysis was undertaken to investigate subsets of T-cells. Serological analysis for CMV was undertaken from samples collected at T0.
RESULTS:
At T0, 66% of the patients and controls were CMV immunoglobulin G-positive. CMV-IgG positive patients had a significantly more rapid increase in IMT at T1.5, compared with controls and CMV-IgG negative patients. CMV-IgG positive patients had a significantly higher percentage of T-cells lacking CD28 (both CD4+CD28null and CD8+CD28null T-cells) than CMV-IgG negative patients. Increased levels of CD4+CD28null and CD8+CD28null T-cells were significantly associated with IMT at T11, adjusted for systolic blood pressure. CX3CR1 was expressed in CD4+ and CD8+ CD28null T-cells, but CX3CR1 per se was not associated with increased IMT.
CONCLUSIONS:
Presence of CMV IgG-antibodies in patients with RA is associated with altered T-cell-populations and an increased burden of atherosclerosis. A possible protective effect of antiviral treatment in CMV-positive patients with new-onset RA should be considered.
