Background: Rheumatoid arthritis (RA) is a systemic inflammatory disorder, with the most common extra-articular manifestation being interstitial lung disease (ILD), which requires deeper exploration in identifying reliable biomarkers for early diagnosis, monitoring, and treatment assessment.

Objectives: This study analyzes dynamic metabolomic changes during the disease course of RA-ILD.

Methods: Serum samples were collected from 69 patients with RA-ILD, 25 no-RA-ILD, and 25 healthy controls (HC) for metabolomics. As for RA-ILD, three key phases relative to ILD were focused: the pre-ILD phase, the early phase (≤ 2 years post-diagnosis), and the late phase (> 2 years post-diagnosis). Short Time-series Expression Miner (STEM) analysis was used to identify differential metabolites, enriched pathways, and significant temporal patterns.

Results: Compared with HC, RA exhibited 1004 differential metabolites (642 up-regulated, 362 down-regulated), enriched in pathways such as mitochondrial beta-oxidation of short chain saturated fatty acid and sphingolipid metabolism. From the above metabolites, 476 significantly differential metabolites (288 up-regulated, 188 down-regulated) were identified in RA-ILD compared with no-RA-ILD, primarily enriched in tryptophan metabolism and arachidonic acid metabolism. STEM analysis revealed a significantly distinct temporal pattern (P = 0.002), including three main pathways: arachidonic acid metabolism, retinol metabolism, and alpha linolenic acid and linoleic acid metabolism. There were 12 metabolites such as leukotriene B4, 11,12-epoxyeicosatrienoic acid, thromboxane B2, and eicosapentaenoic acid in this pattern. Compared with both HC and no-RA-ILD, these 12 metabolites were significantly elevated in RA-ILD and showed a continuous decline over time.

Conclusions: This study demonstrates three abnormal activated pathways: arachidonic acid metabolism, retinol metabolism, and alpha linolenic acid and linoleic acid metabolism in the development of RA-ILD, aiding early diagnosis and treatment response.

REFERENCES: NIL.

Acknowledgments: NIL.

Disclosure of Interests: None declared.