Serum proteomics analysis of biomarkers for evaluating clinical response to MTX/IGU therapy in early rheumatoid arthritis

Methotrexate (MTX) and iguratimod (IGU) are conventional synthetic disease modifying antirheumatic drugs widely used in the treatment of Rheumatoid arthritis (RA) in China. Although MTX combined with IGU can significantly inhibit the progression of RA, some patients do not respond to the treatment. The purpose of this study is to explore the difference of serum protein expression between RA patients with good and poor response to the combined therapy by label-free quantitative proteomic approach. From the proteomics data, a total of 782 proteins in the serum of RA patients were detected, and of which 9 were upregulated and 18 were downregulated in the good response group compared to poor response group. Among them, four significantly differentially expressed proteins (RELN, LDHA, MRC1 and TKT) were further validated by multiple reaction monitoring (MRM)-based quantification approach, and three of them (RELN, LDHA and MRC1) were confirmed to be correlated with the response to MTX/IGU therapy. Logistic regression and ROC analysis indicated that the combination of RELN, LDHA and MRC1 had good performance in evaluating the response. This result proved the different serum proteins signature fingerprint between response group and non-response group; and highlighted the potential of the label-free and mass spectrometry-based quantitative proteomic approach in screening bio-markers for evaluating clinical response to MTX/IGU therapy in RA.