Short telomere length is associated with disease progression in rheumatoid arthritis-associated interstitial lung disease

<bold>Background:</bold> Short leukocyte telomere length (LTL) is associated with interstitial lung disease (ILD) occurrence in rheumatoid arthritis (RA). It is also associated with increased mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We hypothesized that short LTL impacts RA-ILD prognosis. <bold>Aim:</bold> To investigate the prognostic value of LTL in RA-ILD. <bold>Methods:</bold> Patients diagnosed with RA-ILD following multidisciplinary assessment were prospectively enrolled in a French national observational study. LTL was measured at enrolment using qPCR in all patients. Short LTL was defined as an age-adjusted LTL<10th percentile. Progression was defined as death or lung transplantation or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ⩾ 5%pred. or transfer capacity (TLCO) ⩾ 10%pred.) within 1 year after enrolment. <bold>Results:</bold> Among 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82%pred. vs 93%pred.) and TLCO (49%pred. vs 63%pred.) at enrolment, and greater 1-year decline in FVC (−4±9%pred. vs 0±8%pred.). ILD patterns on chest CT were similar (UIP for 58% in short LTL vs 48%). RA-ILD progression was observed in 33 patients (33%). Compared to non-progressors, progressors had more frequently a short LTL (61% vs 34%, p univariate =0.011) and lower FVC at enrolment. Multivariate logistic regression identified short LTL and FVC at enrolment as independent predictors of progression (OR 2.90 [1.05-8.36] p=0.042 and OR 0.97 [0.94, 0.996] p=0.030, respectively). <bold>Conclusions:</bold> Short LTL is associated with poorer 1-year outcomes in RA-ILD.

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.oa3787
Primary Topic
Telomeres, Telomerase, and Senescence
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article
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article

Short telomere length is associated with disease progression in rheumatoid arthritis-associated interstitial lung disease

Esther Ebstein, Nathalie Saidenberg-Kermanac’h, Letícia Kawano-Dourado, S. Marchand‐Adam et al.
Telomeres, Telomerase, and Senescence
article

Short telomere length is associated with disease progression in rheumatoid arthritis-associated interstitial lung disease

Esther Ebstein, Nathalie Saidenberg-Kermanac’h, Letícia Kawano-Dourado, S. Marchand‐Adam, Marie‐Christophe Boissier, Benjamin Granger, Hilario Nunès, Christophe Richez, Caroline Kannengiesser, Bruno Crestani, Thierry Schaeverbeke, Stefania Ottaviani, Kinan El Husseini, Raphaël Borie, Jérôme Avouac, Pierre‐Antoine Juge, René‐Marc Flipo, Joyce Lee, Philippe Dieudé
article en

Abstract

<bold>Background:</bold> Short leukocyte telomere length (LTL) is associated with interstitial lung disease (ILD) occurrence in rheumatoid arthritis (RA). It is also associated with increased mortality in idiopathic pulmonary fibrosis, which shares similarities with RA-ILD. We hypothesized that short LTL impacts RA-ILD prognosis. <bold>Aim:</bold> To investigate the prognostic value of LTL in RA-ILD. <bold>Methods:</bold> Patients diagnosed with RA-ILD following multidisciplinary assessment were prospectively enrolled in a French national observational study. LTL was measured at enrolment using qPCR in all patients. Short LTL was defined as an age-adjusted LTL<10th percentile. Progression was defined as death or lung transplantation or functional respiratory decline (absolute decrease in forced vital capacity (FVC) ⩾ 5%pred. or transfer capacity (TLCO) ⩾ 10%pred.) within 1 year after enrolment. <bold>Results:</bold> Among 101 patients with RA-ILD, 46% were male, mean age at enrolment was 66±10 years and 43 (43%) had short LTL. Patients with short LTL had lower FVC (82%pred. vs 93%pred.) and TLCO (49%pred. vs 63%pred.) at enrolment, and greater 1-year decline in FVC (−4±9%pred. vs 0±8%pred.). ILD patterns on chest CT were similar (UIP for 58% in short LTL vs 48%). RA-ILD progression was observed in 33 patients (33%). Compared to non-progressors, progressors had more frequently a short LTL (61% vs 34%, p univariate =0.011) and lower FVC at enrolment. Multivariate logistic regression identified short LTL and FVC at enrolment as independent predictors of progression (OR 2.90 [1.05-8.36] p=0.042 and OR 0.97 [0.94, 0.996] p=0.030, respectively). <bold>Conclusions:</bold> Short LTL is associated with poorer 1-year outcomes in RA-ILD.

Inserm (FR), Délégation Paris 7 (FR), Université Paris Cité (FR), Centre Hospitalier Universitaire de Bordeaux (FR), Centre Hospitalier Universitaire de Lille (FR), Sorbonne Université (FR), Lille’s Cardiology Hospital (FR), Université Sorbonne Paris Nord (FR), Hôpital Cochin (FR), Centre Hospitalier Universitaire de Tours (FR), Assistance Publique – Hôpitaux de Paris (FR), Thion Medical (France) (FR), Hôpital Avicenne (FR), Institut Pierre Louis d‘Épidémiologie et de Santé Publique (FR), Hôpital Bichat-Claude-Bernard (FR), University of Colorado Denver (US)
Good health and well-being
Openalex Percentile: Top 72%
Telomeres, Telomerase, and Senescence
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