Serum metabolomic and lipidomic profiling identifies diagnostic biomarkers for seropositive and seronegative rheumatoid arthritis patients

Hemi Luan, Wanjian Gu, Hua Li, Zi Wang, Lu Lu, Mengying Ke, Jiawei Lu, Wenjun Chen, Zhangzhang Lan, Yanlin Xiao, Jinyue Xu, Yi Zhang, Zongwei Cai*, Shijia Liu*, Wenyong Zhang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

29 Citations (Scopus)


Background: Diagnosing seronegative rheumatoid arthritis (RA) can be challenging due to complex diagnostic criteria. We sought to discover diagnostic biomarkers for seronegative RA cases by studying metabolomic and lipidomic changes in RA patient serum. Methods: We performed comprehensive metabolomic and lipidomic profiling in serum of 225 RA patients and 100 normal controls. These samples were divided into a discovery set (n = 243) and a validation set (n = 82). A machine-learning-based multivariate classification model was constructed using distinctive metabolites and lipids signals. Results: Twenty-six metabolites and lipids were identified from the discovery cohort to construct a RA diagnosis model. The model was subsequently tested on a validation set and achieved accuracy of 90.2%, with sensitivity of 89.7% and specificity of 90.6%. Both seropositive and seronegative patients were identified using this model. A co-occurrence network using serum omics profiles was built and parsed into six modules, showing significant association between the inflammation and immune activity markers and aberrant metabolism of energy metabolism, lipids metabolism and amino acid metabolism. Acyl carnitines (20:3), aspartyl-phenylalanine, pipecolic acid, phosphatidylethanolamine PE (18:1) and lysophosphatidylethanolamine LPE (20:3) were positively correlated with the RA disease activity, while histidine and phosphatidic acid PA (28:0) were negatively correlated with the RA disease activity. Conclusions: A panel of 26 serum markers were selected from omics profiles to build a machine-learning-based prediction model that could aid in diagnosing seronegative RA patients. Potential markers were also identified in stratifying RA cases based on disease activity.

Original languageEnglish
Article number500
JournalJournal of Translational Medicine
Issue number1
Publication statusPublished - 7 Dec 2021

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

  • Lipidomic
  • Metabolomic
  • Rheumatoid arthritis
  • Seronegative


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