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

Project lead
J Lord
University of Birmingham
J.M.Lord@bham.ac.uk
J.M.Lord@bham.ac.uk
2018–2021
FOREUM research grant: € 599,881

Meet the team

J Lord
University of Birmingham
J.M.Lord@bham.ac.uk
K Raza
University of Birmingham
A Pratt
University of Newcastle
A Catrina
Karolinska Institutet
L Padyukov
University of Birmingham
L Mirbahai
University of Birmingham
A van der Helm-van Mil
UMC Leiden
S W Jones
University of Birmingham
N Duggal
University of Birmingham

Objectives

We hypothesise that environmental factors such as smoking and genetic predisposition can cause premature ageing leading to an aged epigenome signature, driving immunesenescence and RA pathogenesis. DNA methylation at 350 specific sites, termed the epigenetic clock, has been identified as an indicator of biological age. We will analyse existing data from patients with established RA and generate new data from very early RA cohorts across Europe to determine if the DNA methylation signature shows advanced ageing in RA patients and if this occurs in the earliest stages of the disease. We will also assess immune phenotype at the various stages of disease development to see if this occurs early or is a consequence of disease.

Patient voice

We have discussed the proposal with a patient group in Birmingham, they thought the idea novel and worthwhile. We gained their input to the lay summary. We will have patient representatives at each site to support the writing of our patient information sheets and to help communicate the findings of the project.

Interim results

The interim data suggest that thymic atrophy, increased neutrophil and regulatory monocyte counts occur early in disease, but the build up of senescent cells is more likely a consequence of disease. We have also completed analysis of published data on DNAm in established RA and the manuscript will be submitted in late April.