Abstract
Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05), representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40). This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023). On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and indicate that they are notably drug-specific.
Highlights
Rheumatoid arthritis (RA) is a chronic disease involving autoimmune reactivity and inflammation of multiple symmetric peripheral joints causing important disability and accompanied of other manifestations and significant life shortening [1]
Biomarkers identify patients that fail to respond to any biological DMARD (bDMARD), and they will not be useful for guiding therapeutic choices
This drug-specificity is supported by the available evidence, which shows that most proposed biomarkers of prediction of response to treatment in RA are informative for some bDMARD but not for others
Summary
Rheumatoid arthritis (RA) is a chronic disease involving autoimmune reactivity and inflammation of multiple symmetric peripheral joints causing important disability and accompanied of other manifestations and significant life shortening [1]. Biomarkers identify patients that fail to respond to any bDMARD, and they will not be useful for guiding therapeutic choices These ideas are disputable because differences between the drug molecules, their routes of administration and doses in addition to the molecular target could lead to specificity on biomarkers [5,6,7,8]. We performed a shotgun proteomic discovery study of response to adalimumab (ADA) using exactly the same procedure we have applied previously for analyzing the response to infliximab (IFX) [16], and subsequently we compared the results obtained with these two anti-TNF monoclonal antibodies This is necessary because there are not any shotgun proteomic study to identify predictive biomarkers in RA apart from two addressing response to IFX [16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
