title: Identification of 7 Proteins in Sera of RA Patients with Potential to Predict ETA/MTX Treatment Response.
abstract: OBJECTIVE
  The recent growth of innovating biologics has opened fascinating avenues for the management of patients. In rheumatoid arthritis, many biologics are currently available, the choice of which being mostly determined empirically. Importantly, a given biologic may not be active in a fraction of patients and may even provoke side effects. Here, we conducted a comparative proteomics study in attempt to identify a predictive theranostic signature of non-response in patients with rheumatoid arthritis treated by etanercept/methotrexate combination.
  
  
  METHODS
  A serum sample was collected prior to treatment exposure from a cohort of 22 patients with active RA. A proteomic "label free" approach was then designed to quantitate protein biomarkers using mass spectrometry. To verify these results, a relative quantification followed by an absolute quantification of interesting protein candidates were performed on a second cohort. The criterion of judgment was the response to etanercept/methotrexate combination according to the EULAR criteria assessed at 6 months of treatment.
  
  
  RESULTS
  These investigations led to the identification of a set of 12 biomarkers with capacity to predict treatment response. A targeted quantitative analysis allowed to confirm the potential of 7 proteins from the latter combination on a new cohort of 16 patients. Two highly discriminating proteins, PROS and CO7, were further evaluated by ELISA on this second cohort. By combining the concentration threshold of each protein associated to a right classification (responders vs non-responders), the sensitivity and specificity reached 88.9 % and 100 %, respectively.
  
  
  CONCLUSIONS
  Prior to methotrexate/etanercept treatment, abundance of several sera proteins, notably PROS and CO7, were associated to response status of RA patients 6 month after treatment initiation.
authors.affiliation: 1. INSERM, U905, Rouen, France ; 2. CNRS, UMR6270, Mont Saint Aignan, France ; 3. PISSARO Proteomic Platform, Mont Saint Aignan, France ; 4. Normandy University, IRIB, Rouen, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Obry
authors.affiliation: 2. CNRS, UMR6270, Mont Saint Aignan, France ; 3. PISSARO Proteomic Platform, Mont Saint Aignan, France ; 4. Normandy University, IRIB, Rouen, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.affiliation: 1. INSERM, U905, Rouen, France ; 4. Normandy University, IRIB, Rouen, France ; 5. Department of Rheumatology, Rouen University Hospital, Rouen, France ; 6. CIC/CRB1404, Rouen University, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lequerré
authors.affiliation: 2. CNRS, UMR6270, Mont Saint Aignan, France ; 3. PISSARO Proteomic Platform, Mont Saint Aignan, France ; 4. Normandy University, IRIB, Rouen, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jarnier
authors.affiliation: 1. INSERM, U905, Rouen, France ; 4. Normandy University, IRIB, Rouen, France ; 7. Department of Immunology, Rouen University Hospital, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.affiliation: 8. Department of Rheumatology, Amiens University Hospital, Amiens, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Fardellone
authors.affiliation: 9. Department of Rheumatology, Lille University Hospital, Lille, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Philippe
authors.affiliation: 10. Department of Rheumatology, Caen University Hospital, Caen, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Marcelli
authors.affiliation: 1. INSERM, U905, Rouen, France ; 4. Normandy University, IRIB, Rouen, France ; 5. Department of Rheumatology, Rouen University Hospital, Rouen, France ; 6. CIC/CRB1404, Rouen University, Rouen, France.
authors.forename: Xavier Le
authors.initials: XL
authors.lastname: Loët
authors.affiliation: 1. INSERM, U905, Rouen, France ; 4. Normandy University, IRIB, Rouen, France ; 5. Department of Rheumatology, Rouen University Hospital, Rouen, France ; 6. CIC/CRB1404, Rouen University, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vittecoq
authors.affiliation: 2. CNRS, UMR6270, Mont Saint Aignan, France ; 3. PISSARO Proteomic Platform, Mont Saint Aignan, France ; 4. Normandy University, IRIB, Rouen, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis*; D016903:Drug Monitoring / Q000379:methods*; D000068800:Etanercept / Q000008:administration & dosage*; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage*; D012680:Sensitivity and Specificity
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D001798:Blood Proteins; D000068800:Etanercept; D008727:Methotrexate
keywords: biomarkers; rheumatoid arthritis