Associations between Shortened Telomeres and Rheumatoid Arthritis-Associated Interstitial Lung Disease Among U.S. Veterans

Abstract

Background: Shortened telomeres are associated with several different subtypes of interstitial lung disease (ILD), although studies of telomere length and ILD in rheumatoid arthritis (RA) are lacking.

Methods: Within the Veterans Affairs Rheumatoid Arthritis (VARA) registry, we performed cross-sectional and case-control studies of prevalent and incident ILD, respectively. We randomly selected a subset of RA patients with ILD and individually matched them to RA patients without ILD according to age, sex, and VARA enrollment date. Telomere length was measured on peripheral blood leukocytes collected at registry enrollment using quantitative PCR (T/S ratio). Short telomeres were defined as a T/S ratio in the lowest 10th percentile of the cohort.

Results: Our cross-sectional study cohort was comprised of 54 RA-ILD patients and 92 RA-non-ILD patients. T/S ratios significantly differed between patients with and without prevalent ILD (1.56 [IQR 1.30, 1.78] vs. 1.96 [IQR 1.65, 2.27], p<0.001). Similarly, prevalence of ILD was significantly higher in patients with short vs. normal-length telomeres (73.3% vs. 32.8%, p=0.002). Short telomeres were independently associated with an increased odds of prevalent ILD compared to normal-length telomeres (adjusted OR 6.60, 95% CI 1.78-24.51, p=0.005). In our case-control analysis, comprised of 22 incident RA-ILD cases and 36 RA-non-ILD controls, short telomeres were not associated with incident RA-ILD (adjusted OR 0.90, 95% CI 0.06-13.4, p=0.94).

Conclusion: Short telomeres were strongly associated with prevalent but not incident ILD among patients with RA. Additional studies are needed to better understand telomere length dynamics among RA patients with and without ILD.

Note:
Funding Information: This work was supported by the National Heart, Lung, and Blood Institute, grant numbers T32HL007891 (JGN) and K24HL103844 (SMK), VA Clinical Science Research and Development, grant numbers CX001703 (JFB) and CX002203 (BRE), VA Biomedical Laboratory Research and Development, grant number BX004600 (TRM), U.S. Department of Defense, grant number PR200793 (BRE), and the National Institute of General Medical Sciences, grant number U54GM115458 (BRE, TRM).

Declaration of Interests: None to report. Specifically, JGN, JFB, QC, NS, TDM, PR, GMT, BCS, TRM, and FBJ and have no relevant conflicts of interest. BRE has received consulting fees from Boehringer Ingelheim unrelated to this project. SMK has received consulting fees from Acceleron Pharma, United Therapeutics Corporation, and VIVUS unrelated to this project and holds stock in AbbVie.

Ethics Approval Statement: The present study was approved by the VARA Scientific Ethics and Advisory Committee. All patients provided informed consent prior to enrollment.

Keywords: Interstitial lung disease, rheumatoid arthritis, rheumatoid arthritis-associated interstitial lung disease, telomere length, telomeres, T/S ratio