{Reference Type}: Journal Article {Title}: Proteomics analyses of human plasma reveal triosephosphate isomerase as a potential blood marker of methotrexate resistance in rheumatoid arthritis. {Author}: Escal J;Neel T;Hodin S;Boussoualim K;Amouzougan A;Coassy A;Locrelle H;Thomas T;Delavenne X;Marotte H; {Journal}: Rheumatology (Oxford) {Volume}: 63 {Issue}: 5 {Year}: 2024 May 2 {Factor}: 7.046 {DOI}: 10.1093/rheumatology/kead390 {Abstract}: OBJECTIVE: The objective of this study was to assess differentially expressed blood proteins between patients with active RA and patients in remission after MTX treatment, with the aim of identifying a biomarker of MTX resistance (MTXR).
METHODS: Two populations of RA patients treated with a stable dose of s.c. 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 eight plasma proteins that were differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors in 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 biomarkers of MTXR, with the identification of two actors in 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.