Short telomeres associated with prevalent ILD in rheumatoid arthritis

Short telomeres were strongly associated with prevalent interstitial lung disease among patients with rheumatoid arthritis, according to cross-sectional study results published in Respiratory Medicine.

However, results of a case-control analysis did not show this same association for incident ILD.

“Telomeres are the protective ‘caps’ on the ends of chromosomes, which, when sufficiently long, prevent the activation of DNA damage responses that result in cellular senescence or apoptosis,” Jake G. Natalini, MD, transplant pulmonologist in the division of pulmonary, critical care and sleep medicine in the department of medicine at New York University Grossman School of Medicine, New York, and colleagues wrote. “Telomeres tend to shorten with age and various cellular injuries, and shortened telomeres have been associated with both familial and sporadic [idiopathic pulmonary fibrosis].”

Researchers conducted a cross-sectional study of 54 randomly selected patients with rheumatoid arthritis-associated ILD within the Veterans Affairs Rheumatoid Arthritis registry. These patients were individually matched to 92 randomly selected patients with rheumatoid arthritis without ILD according to age, sex and Veterans Affairs Rheumatoid Arthritis enrollment date.

Researchers measured telomere length on peripheral blood leukocytes collected at registry enrollment and short telomeres were defined as a T/S ratio, or the telomeric repeat copy signal to reference single-copy gene (human beta globin) signal ratio, in the lowest 10th percentile of the patient cohort.

There were significantly different T/S ratios between patients with (1.56; 95% CI, 1.3-1.78) and without (1.96; 95% CI, 1.65-2.27) prevalent ILD (P < .001). Researchers observed significantly higher ILD prevalence among patients with short telomeres compared with patients with normal-length telomeres (73.3% vs. 32.8%; P = .002).

Having short telomeres was independently associated with an increased odds of prevalent ILD compared with having normal-length telomeres (adjusted OR = 6.6; 95% CI, 1.78-24.51).

In addition, researchers also conducted a nested case-control study of incident rheumatoid arthritis-associated ILD within the Veterans Affairs Rheumatoid Arthritis registry using the same 92 patients with rheumatoid arthritis and no ILD at baseline. Among them, researchers identified 22 cases of incident ILD; 36 patients with at least 6 years of follow-up data from registry enrollment were included as controls.

In the case-control analysis, researchers observed no association between short telomeres and incident rheumatoid arthritis-associated ILD (aOR =0.9; 95% CI, 0.06-13.4).

“Additional longitudinal studies are needed to better characterize telomere dynamics among [rheumatoid arthritis] patients with and without ILD,” the researchers wrote.