1122: Short Peripheral Blood Leukocyte Telomere Length in Rheumatoid Arthritis - Interstitial Lung Disease

Pierre-Antoine Juge¹, Tracy Doyle², Seoyeon Lee³, Avram Walts⁴, Anthony Esposito⁵, Sergio Poli de Frias⁶, Ritu R. Gill⁷, Hiroto Hatabu⁸, Mizuki Nishino⁸, Michael Weinblatt⁹, Nancy A. Shadick⁶, Kristen Demoruelle¹⁰, Ivan O. Rosas¹¹, Benjamin granger¹², Kevin D Deane¹³, Bruno Crestani¹⁴, Paul Wolters¹⁵, Philippe Dieude¹⁶ and Joyce Lee¹³, ¹Rheumatology department, Bichat Hospital, Paris, France, ²Brigham and Women's Hospital, Boston, MA, ³Department of Medicine, University of California, San Francisco, CA, ⁴Department of medicine, National Jewish Hospital, Denver, CO, ⁵Brigham and Women's Hospital, Department of Medicine, Boston, MA, ⁶Department of Medicine, Brigham and Women's Hospital, Boston, MA, ⁷Beth Israel Deaconess Medical Center, Radiology Department, Boston, MA, ⁸Department of Radiology, Brigham and Women's Hospital, Boston, MA, ⁹Brigham and Women's Hospital, Harvard Medical School, Boston, MA, ¹⁰Department of Medicine, University of Colorado, Denver, CO, ¹¹Baylor College of Medicine, Houston, TX, ¹²Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, PEPITES, F75013, Paris, France, Paris, France, ¹³University of Colorado Denver Anschutz Medical Campus, Denver, CO, ¹⁴Hopital Bichat, Paris University, Paris, France, ¹⁵UCSF, SF, ¹⁶Université Paris Cité, Paris, France

Background/Purpose: Shortened telomere lengths (TL) have been associated with interstitial lung disease (ILD), in particular idiopathic pulmonary fibrosis (IPF). Given the phenotypic overlap between IPF and rheumatoid arthritis (RA)-associated ILD, it is not surprising that mutations in telomerase-related genes have been found in 12% of individuals with RA-ILD. Our objective was to determine if shortened TL is associated with ILD in individuals with RA.

Methods: In this case-control study, TL was measured using quantitative PCR of DNA isolated from peripheral blood leukocytes (PBL) of individuals with RA with and without ILD in the derivation and replication groups. Unadjusted and adjusted regression models assessed the strength of the association between ILD status and PBL-TL and between PBL-TL disease severity.

Results: In the derivation population, age and sex adjusted PBL-TL (OR 0.003, p< 0.001) was associated with RA-ILD (n=150) compared to RA no ILD (n=205). This was replicated in 109 subjects with RA-ILD and 86 with RA-noILD (OR 0.001, p< 0.001). In all 550 RA subjects, mean PBL-TL was shorter in RA-ILD compared with RA-noILD and after adjustment for age, sex, smoking status, RA duration and ever methotrexate use (OR 0.01, p< 0.001) (Figure1). Among individuals with RA-ILD (n=259), PBL-TL was associated with baseline forced vital capacity percent predicted in both unadjusted and adjusted models.

Conclusion: Shortened PBL-TL is associated with ILD in individuals with RA and with baseline disease severity among individuals with RA-ILD. These findings suggest that telomere shortening may contribute to the pathogenesis of RA-ILD.
Figure 1: RA-ILD cases positioned on a nomogram of telomere length in RA-ILD (○) and RA-noILD (+) as a function of square root of age in controls with RA-noILD.
Disclosures: P. Juge, Bristol-Myers Squibb(BMS), Novartis, AstraZeneca, Boehringer-Ingelheim; T. Doyle, Bristol-Myers Squibb(BMS), Boehringer-Ingelheim, L.E.K. Consulting, Genentech; S. Lee, None; A. Walts, None; A. Esposito, None; S. Poli de Frias, None; R. Gill, None; H. Hatabu, None; M. Nishino, None; M. Weinblatt, Eli Lilly, AbbVie/Abbott, aclaris, Amgen, Bristol-Myers Squibb(BMS), corevitas, Eqrx, genosco, GlaxoSmithKlein(GSK), Gilead, horizon therapeutics, johnson and johnson, scipher, canfite, inmedix; N. Shadick, None; K. Demoruelle, None; I. Rosas, None; B. granger, Bristol-Myers Squibb(BMS); K. Deane, Werfen; B. Crestani, Roche, Boehringer-Ingelheim; P. Wolters, None; P. Dieude, None; J. Lee, None.