Finally, S100A9 protein acts as an independent predictor when compared to standard biomarkers. Previously restricted to the simple identification of protein sample, the recent progresses in mass spectrometry allow the quantification of MLN4924 proteins within complex matrices. The so-called “label free” approach enables protein relative quantification in several samples based on the comparison of intensities of peptide ion currents observed during LC separations. This challenging technology is accurate and robust enough to estimate protein ratios after adequate statistical processing. Although initiated to draw a global picture, this work was focused on two proteins of interest, namely S100A8 and S100A9 proteins. These two proteins are constitutively expressed in neutrophils and monocytes but also in macrophages during acute or chronic inflammation. They are associated with various infectious or inflammatory diseases. Recently, some studies have shown that biological therapies modulate the expression of S100 proteins. Indeed, the expression of several genes, including those coding for S100A12 and S100A8 proteins was lower in PBMCs after treatment with etanercept or adalimumab. Besides, the level of soluble calprotectin was shown to decrease and to be associated to ultrasonographic synovitis scores in RA patients treated by adalimumab. Thus, calprotectin might be of additional value in the assessment of RA patients under biologic treatment. However, even though levels of S100 proteins appear to be influenced by TBAs, their theranostic value has never been demonstrated until now. So far, these proteins have only been identified as diagnostic and prognostic markers of RA. Furthermore, these proteins are found at high concentrations in the serum of RA patients. A high correlation is observed between flares and elevated concentration of these proteins, making the latter interesting inflammatory markers, reflecting the disease activity. Here, proteomic investigations were firstly performed with PBMCs because these cells and several cytokines produced by them have a pivotal role in RA pathogenesis and are targeted by ETA. Specifically, in the context of RA, PBMCs constitute an advantageous surrogate tissue as they allow for screening in any subject, whereas synovium is only accessible through an invasive procedure. Additionally, proteomic investigations on PBMCs benefit from a reduced dynamic range of protein concentration compared to serum. The results of this first part of the study demonstrated a similar over-expression of S100A8 and S100A9 proteins in the cellular PBMC proteome, where they might appear as a heterodimeric complex. Thereafter, we investigated the “theranostic” potential of S100 proteins in sera from R and NR patients to ETA/MTX combination. In contrast to PBMC investigations, this study only revealed a significant overexpression of the S100A9 protein in R patients, confirmed by ELISA absolute quantification. Conversely, ELISA revealed a similar expression of S100A8 and calprotectin in both R and NR groups.