Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Interstitial lung disease (ILD) is one of the leading causes of mortality for rheumatoid arthritis (RA) patients. Despite its high prevalence and mortality, little is known about the pathogenesis of RA–associated ILD (RA-ILD). Given that idiopathic pulmonary fibrosis (IPF) and RA–ILD share the usual interstitial pneumonia pattern and common environmental risk factors such as tobacco smoking, we hypothesized that the two diseases may share additional risk factors including familial pulmonary fibrosis (FPF) susceptibility genes.
Methods: We used whole-exome sequencing (WES) followed by restricted analysis of a discrete number of FPF-linked genes to compare mutations among consecutive RA–ILD patients collected by a French network of pulmonologists and rheumatologists. A burden test was used to assess the excess number of mutations in RA–ILD patients.
Results: Among the 101 RA–ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA–ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations for RA–ILD patients compared to controls (p=9.45x10–4, odds ratio [OR] 3.17 95% CI 1.53–6.12). Telomeres were shorter for RA-ILD patients with a TERT, RTEL1 or PARN mutation than controls (p=2.87×10-2).
Conclusion: Our results support the contribution of FPF-linked genes to RA–ILD susceptibility, linking RA–ILD and IPF pathogeneses. Recent therapeutic advances in IPF may open new avenues for treatment of ILD, the most severe RA manifestation for which effective drugs are lacking.
To cite this abstract in AMA style:Juge PA, Borie R, Kannengiesser C, Gazal S, Revy P, Wemeau-Stervinou L, Debray MP, Ottaviani S, Adam-Marchand S, Nathan N, Thabut G, Richez C, Nunes H, Callebaut I, Justet A, Leulliot N, Bonnefond A, Salgado D, Richette P, Desvignes JP, Lioté H, Froguel P, Allanore Y, Sand O, Dromer C, Flipo RM, Clément A, Béroud C, Sibilia J, Coustet B, Cottin V, Boissier MC, Wallaert B, Schaeverbeke T, Dasto le Moal F, Frazier A, Ménard C, Soubrier M, Saidenberg N, Valeyre D, Amselem S, Boileau C, Crestani B, Dieudé P. Shared Genetic Predisposition in Rheumatoid Arthritis–Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis: A Genetic Association Study [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/shared-genetic-predisposition-in-rheumatoid-arthritis-interstitial-lung-disease-and-idiopathic-pulmonary-fibrosis-a-genetic-association-study/. Accessed November 28, 2020.
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