Does accelerated epigenetically defined ageing, including immune ageing, contribute to RA pathogenesis? Interaction in the development of RA
Concept
Age is a major risk factor for rheumatoid arthritis (RA), yet we understand little of the role ageing processes play in RA pathogenesis. Why this matters is that if ageing processes are a driver for RA, then improved understanding of the mechanisms involved may reveal innovative approaches to prevention or early treatment of this disease.
Facts and Figures
J Lord
University of Birmingham
J.M.Lord@bham.ac.uk
Meet the Team
University of Birmingham
University of Newcastle
University of Birmingham
University of Birmingham
UMC Leiden
University of Birmingham
University of Birmingham
Final Results
Rheumatoid arthritis (RA) is more common with advancing age and the immune system of patients with RA show signs of ageing at an earlier age than healthy adults. This project had two objectives, to determine: 1. If those adults who develop RA are biologically older than those who do not; 2) Whether an aged immune system is a cause or consequence of RA. Results show that overall adults with RA are not biologically older than healthy adults. However, biological age was higher in RA patients of South Asian origin, though numbers were small and this finding needs confirmation. Through analysis of primary care data we also showed that a wide range of immune mediated inflammatory diseases, including RA, occur much earlier in non-white populations. For objective 2, the study found signs of an aged immune system in adults at risk of developing RA, namely those with arthralgia and undifferentiated arthritis.
Lay Summary
Rheumatoid arthritis (RA) is more common in old age and the immune system plays a role in causing the disease. In particular RA is associated with inflammation in the joints and with immune cells attacking tissues in the joint, called autoimmunity. As we age our immune system becomes more prone to inflammation and autoimmunity. This project set out to answer two questions: 1. Are those adults who develop RA biologically older than those who do not; 2) Is an aged immune system a cause or consequence of RA.
The project determined the biological age of twins, one who had RA and one who did not, by analysing their DNA. In general, adults with RA were not biologically older than healthy adults. However, RA patients of South Asian ethnicity were biologically older than healthy South Asian adults. The study also looked at how old patients were when they developed RA and found that non-white patients were approximately 7 years younger than white patients. These findings suggest that the disease may have some different causes in non-white populations.
For the second question, the results show that some signs of an aged immune system were seen in adults at risk of developing RA, namely those with arthralgia and undifferentiated arthritis, and so this may be one cause of RA. These results are promising as there are studies that have identified drugs that can rejuvenate the immune system, this could be a new way to prevent or treat RA in its early stages.
Publications
- Sharma-Oates A, Zemedikun DT, Kumar K, Reynolds JA, Jain A, Raza K, Williams JA, Bravo L, Cardoso VR, Gkoutos G, Nirantharakumar K, Lord JM. Early onset of immune-mediated diseases in minority ethnic groups in the UK. BMC Med. 2022 Oct 13;20(1):346. doi: 10.1186/s12916-022-02544-5. PMID: 36224602; PMCID: PMC9558944.
Patient Voice
The project will include patient representatives at each site to support the writing of the patient information sheets and to help communicate the findings of the project. Close work with a patient group in Birmingham.
