Rheumatoid arthritis (RA) is associated with reduced lifespan and shortened telomere length in lymphocytes but the mechanism underlying this is unclear. Telomere loss in white blood cells is accelerated by oxidative stress and inflammation in vitro. We postulated that accelerated white blood cell telomere shortening in rheumatoid arthritis occurs as a result of exposure to chronic inflammation.
Objectives: To measure telomere terminal restriction fragment (TRF) length in a large cohort of RA cases and healthy controls; to explore associations of TRF length with features of disease and with RA- associated HLA-DRB1 alleles.
Methods: We measured white blood cell (WBC) terminal restriction fragment (TRF) length by Southern blot in DNA from 176 hospital-based RA cases satisfying the 1987 ACR criteria and 1151 healthy controls. We compared TRF length between cases and controls, and assessed the effects of disease duration, severity and HLA-DRB1 alleles encoding the shared epitope (SE).
Results: Age and sex-adjusted TRF length was significantly shorter in RA cases compared to controls (p < 0.001). There was no association between age- and sex-adjusted TRF length and disease duration, CRP or Larsen score. The presence of one or more SE encoding alleles was associated with reduced adjusted TRF length in RA cases (SE positive vs. SE negative cases, p = 0.038) but not in controls.
Conclusion: We have demonstrated reduced TRF length in a large group of RA patients compared to controls. The reduction is apparently independent of disease duration and markers of disease severity but is influenced by HLA-DRB1 genotype.
- Rheumatoid arthritis