Abstract
ObjectivesOne way to optimize the drug prescription in rheumatoid arthritis (RA) is to identify predictive biomarkers of drug responsiveness. Here, we investigated the potential "theranostic" value of proteins of the S100 family by monitoring levels of both S100A8 and S100A9 in blood samples from RA patients.DesignFor proteomic analysis, peripheral blood mononuclear cells (PBMC) and serum samples were collected in patients prior to initiation of the methotrexate/etanercept (MTX/ETA) combination. Firstly, relative mass spectrometry (MS) quantification focusing on S100A8 and S100A9 proteins was carried out from PBMCs samples to identify potential biomarkers. The same approach was also performed from serum samples from responder (R) and non responder (NR) patients. Finally, to confirm these results, an absolute quantification of S100A8, S100A9 proteins and calprotectin (heterodimer of S100A8/S100A9) was carried out on the serum samples using ELISA.ResultsMS analyses revealed that both S100A8 and S100A9 proteins were significantly accumulated in PBMC from responders. In contrast to PBMC, only the S100A9 protein was significantly overexpressed in the serum of R patients. Absolute quantification by ELISA confirmed this result and pointed out a similar expression level of S100A8 protein and calprotectin in sera from both R and NR groups. Thus, the S100A9 protein revealed to be predictive of MTX/ETA responsiveness, contrarily to parameters of inflammation and auto-antibodies which did not allow significant discrimination.ConclusionThis is the first report of an overexpression of S100A9 protein in both PBMCs and serum of patients with subsequent response to the MTX/ETA combination. This protein thus represents an interesting biomarker candidate of therapeutic response in RA.
Highlights
Rheumatoid arthritis (RA) is a chronic, autoimmune disease that results in progressive structural damage and disability
We focused on the expression of S100A9 and S100A8 proteins in RA patients with active disease treated by methotrexate/ etanercept (MTX/ETA) combination to determine the global expression level of those proteins
In the context of a global proteomic approach in peripheral blood mononuclear cells (PBMC) from 6 RA patients treated by the MTX/ETA combination (Population 1), we focused our attention on the abundance levels of S100A9 and S100A8 proteins that were identified as potential theranostic biomarkers among a panel of candidate proteins
Summary
Rheumatoid arthritis (RA) is a chronic, autoimmune disease that results in progressive structural damage and disability. Five TNF blocking agents (TBAs) are available and used as a second line of therapy after inadequate response to methotrexate Even if these biologic agents have improved RA patient care [2, 3, 4], 30% of them do not respond to these innovative biotherapies [5]. The choice of the first biological agent is difficult in practice, and since almost all of them can be used as first line biotherapy after failure of at least one non-biological disease modifying anti-rheumatic drugs (DMARDs) including MTX Considering all these issues, predicting the patient’s response to a given treatment has become a very important challenge. It remains yet difficult to get valuable markers that would predict the drug responsiveness ("theranostic" biomarkers)
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