RESUMEN
OBJECTIVES: To assess differentially expressed blood proteins between patients with active rheumatoid arthritis (RA) and patients in remission after methotrexate (MTX) treatment, with the aim of identifying a biomarker of methotrexate resistance (MTXR). METHODS: Two populations of RA patients treated with a stable dose of subcutaneous MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach. RESULTS: Untargeted proteomics analysis revealed 8 plasma proteins differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors of glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis. CONCLUSIONS: A first step was achieved in the search for biomarker of MTXR with identification of two actors of glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.
