Proteomics analyses of human plasma reveal triosephosphate isomerase as a potential blood marker of methotrexate resistance in rheumatoid arthritis.

This study focused on identifying blood protein biomarkers associated with methotrexate resistance (MTXR) in rheumatoid arthritis (RA) patients by comparing those with active disease to patients in remission after stable subcutaneous methotrexate (MTX) treatment. Using untargeted and targeted proteomics analyses of plasma samples from 56 RA patients, the researchers found eight proteins differentially expressed between the groups, notably two key glycolytic enzymes—triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI)—which were downregulated in patients with active RA. Targeted proteomics confirmed the decreased expression of TPI-1 in active RA, suggesting these glycolytic proteins as potential biomarkers for MTXR. The study recommends further validation in larger, treatment-naive cohorts to assess the predictive value of these proteins for MTX response.