Background: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is an autoimmune condition associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. Metabolic disturbances have been reported in inflammatory myopathies, including DM. However, understanding whether alterations of metabolomics profiling participate in ILD development in MDA5+ DM remains undetermined.

Objectives: In this study, we combined untargeted and targeted metabolomices profiling in the plasma from distinct clinical subtypes of MDA5+ DM, including non-ILD, chronic ILD and RP-ILD, to address this question.

Methods: Untargeted and targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS) to profile metabolites in different MDA5+ DM subtypes and healthy controls (HCs). Then, Kyoto Encyclopedia of Genes and Genomes enrichment analysis (KEGG) analysis and weighted gene co-expression network analysis (WGCNA) were used to identify altered pathways. Univariate and multivariable logistic regression analyses were conducted to confirm the risk and protective metabolites associated with RP-ILD.

Results: The metabolic imbalance in the plasma of MDA5+DM patients mainly affects amino acid metabolism, further analysis showed that there were significant changes focusing on the tryptophan pathway. It is worth noting that compared with the chronic ILD, non-ILD, and HCs subgroups, several key metabolites (tryptophan and Kynurenine) were significantly dysregulated in the RP-ILD subgroup, indicating disrupted tryptophan metabolism. The logistic regression analysis showed that aberrant tryptophan metabolism is a risk factor for RP-ILD in MDA5+ DM patients.

Conclusion: Our results indicated that alterations in the tryptophan metabolism may play an active role in the pathogenesis of RP-ILD in MDA5+ DM and could be considered as a new potential therapeutic avenue.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.