Serum metabolite signature panel may serve as a potential biomarker for the early clinical diagnosis of RA

According to a study published in Frontiers in Immunology, a serum-based biomarker panel comprising glyceric acid, lactic acid, and 3-hydroxysovaleric acid has the potential to aid in the early diagnosis of rheumatoid arthritis (ERA).  

The observational case-control study conducted by Dr. Rodríguez-Muguruza and colleagues performed untargeted metabolomic profiling of serum obtained from 32 patients with ERA and 19 healthy controls. The analysis of the serum metabolites in ERA patients revealed significant differences in the levels of 11 out of 81 metabolites. ROC analysis demonstrated that a combination of three metabolites—glyceric acid, lactic acid, and 3-hydroxyisovaleric acid—could accurately diagnose ERA in 96.7% of patients. This accuracy surpassed that of the anti-cyclic citrullinated peptide (ACPA) based diagnosis by 2.9% and enhanced the preclinical detection of ERA. Dysregulated pathways in ERA patients included aminoacyl-tRNA biosynthesis and serine, glycine, and phenylalanine metabolism. 

Glyceric acid is a product of glycerol oxidation, which can be used to synthesize triacylglycerols through glycerolipid metabolism. This process is increased in patients with pre-clinical and ERA. Lactic acid, an essential organic acid in cellular metabolism, contributes to the progression of RA from the early stages of inflammation to the later stages of bone destruction. Lactate is predominantly produced in the cytoplasm under conditions of hypoxia or during high-throughput glycolysis in rapidly proliferating cells, both of which occur in RA. This explains the increased concentration of lactate in the synovial fluid of RA patients. The third metabolite, 3-hydroxyisovaleric acid, is a by-product of the leucine degradation pathway. Levels of leucine vary with RA disease progression and are associated with factors such as age, sex, and diet. 

 The study suggests that the serum metabolite signature panel, comprising glyceric acid, lactic acid, and 3-hydroxyisovaleric acid, demonstrates higher accuracy than traditional clinical markers like anti-cyclic citrullinated peptide antibodies. Additionally, the use of metabolomics can provide valuable insights into the pathways involved in ERA, potentially leading to the development of new diagnostic and treatment approaches. However, it is important to note that metabolomics is still a relatively new technology in the clinical setting and requires further research. 


Rodríguez-Muguruza S, Altuna-Coy A, Arreaza-Gil V, Mendieta-Homs M, Castro-Oreiro S, Poveda Elices MJ, et al. A serum metabolic biomarker panel for early rheumatoid arthritis. Front Immunol. 2023;14:1253913.