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Review
. 2025 Feb 24:12:1542400.
doi: 10.3389/fmed.2025.1542400. eCollection 2025.

Navigating interstitial lung disease associated with rheumatoid arthritis (RA-ILD): from genetics to clinical landscape

Nicol Bernardinello  1 , Margherita Zen  2 , Gioele Castelli  1 , Elisabetta Cocconcelli  1 , Elisabetta Balestro  1 , Raphaël Borie  3 , Paolo Spagnolo  1
Affiliations
Review

Navigating interstitial lung disease associated with rheumatoid arthritis (RA-ILD): from genetics to clinical landscape

Nicol Bernardinello et al. Front Med (Lausanne). .

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects millions of people worldwide and is characterized by persistent inflammation, pain, and joint destruction. In RA, the dysregulation of the immune system is well documented. However, the genetic basis of the disease is not fully understood, especially when extra-articular organs are involved. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with RA. Notably, RA-ILD shares several risk factors with idiopathic pulmonary fibrosis (IPF), namely male gender, smoking history, usual interstitial pneumonia (UIP) pattern of fibrosis, and association with the MUC5B rs35705950 polymorphism. In addition, other genetic susceptibilities are reported in RA-ILD for some HLA alleles and other less studied polymorphisms. However, the pathobiology of RA-ILD, particularly whether and to what extent genetic and environmental factors interact to determine the disease, remains elusive. In this review, we summarize and critically discuss the most recent literature on the genetics and pathogenesis of RA-ILD. The main clinical aspects of RA-ILD are also discussed.

Keywords: MUC5B; genetics; idiopathic pulmonary fibrosis; interstitial lung disease; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Axial CT scans illustrating the radiological presentation of patients with RA-ILD. (A,B) Usual interstitial pneumonia pattern in two male patients with rheumatoid arthritis. Honeycombing and traction bronchiectasis are visible in both patients. (C) Mild and migrant organizing pneumonia in female patients with rheumatoid arthritis. (D) Mild reticulation in an asymptomatic male patient with RA.
Figure 2
Figure 2
Risk factors associated with the development of ILD in patients with RA. GERD, gastroesophageal reflux. This picture summarizes the most frequent risk factors associated with the development of interstitial lung disease in patients with RA. This image was created by Biorender.com [Bernardinello (2025), https://BioRender.com/q67s977].
See this image and copyright information in PMC

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