RA-ILD: Screening risk and genetic susceptibility Save

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) remains one of the most serious extra-articular manifestations of RA, contributing substantially to morbidity and mortality. Two abstracts presented at EULAR 2026 add important insights into identifying patients at risk for RA-ILD and understanding the genetic mechanisms that may underpin disease development.

The first, from the international ANCHOR-RA study (OP084), addresses a clinically important question: how common is undiagnosed ILD in patients with RA who already have recognised risk factors? In this prospective cross-sectional study across 27 centres in six countries, investigators screened patients with RA who had at least two established RA-ILD risk factors but no prior ILD diagnosis and no recent chest CT imaging. All participants underwent centrally reviewed HRCT scanning.

Among 1169 screened patients, 9.1% were found to have previously undiagnosed ILD. Several factors were associated with ILD on exploratory analyses, including older age, male sex, greater smoking exposure, lower DLco, reduced oxygen saturation, crackles on auscultation, higher DAS28-ESR scores and carriage of the MUC5B promoter variant. Interestingly, extra-articular manifestations were not associated with ILD in this cohort.

The findings reinforce that clinically occult ILD is not uncommon in patients with RA who carry recognised risk factors. Importantly, many of the associated features identified are readily available in routine rheumatology practice, suggesting clinicians may be able to better target screening approaches. The study also further supports the growing role of MUC5B as a genetic risk marker in RA-ILD.

The second abstract (OP088) delves deeper into genetic pre-dispositions to RA-ILD, by further by examining rare deleterious variants in telomere-related genes (TRGs). The investigators analysed whole exome and whole genome sequencing data from French and US cohorts comprising more than 700 RA-ILD cases and nearly 900 RA controls without ILD.

Rare deleterious TRG variants were significantly enriched in RA-ILD compared with RA controls without ILD, with a pooled odds ratio of 2.9. Importantly, this association appeared independent of both smoking and MUC5B status. The magnitude of risk conferred by these variants was comparable to that observed in idiopathic pulmonary fibrosis (IPF), further strengthening the biological parallels between RA-ILD and fibrotic lung disease more broadly.

Notably, the association was present in both UIP and non-UIP imaging patterns, suggesting telomere dysfunction may contribute across the spectrum of RA-ILD phenotypes rather than solely in UIP-pattern disease.

Together, these studies highlight how RA-ILD risk is likely driven by an interplay between clinical, environmental and genetic factors. The ANCHOR-RA data support more proactive identification of at-risk patients, while the telomere study provides further evidence that fibrotic pathways central to IPF may also be highly relevant in RA-ILD.

As the field moves toward earlier detection and potentially earlier intervention for RA-ILD, integrating clinical phenotyping with molecular and genetic risk profiling may become increasingly important in defining who should undergo screening and how aggressively disease should be monitored.