title: Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis.
abstract: OBJECTIVE
  The use of biologicals such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response.
  
  
  METHODS
  Plasma profiles of 60 patients with RA (28 non-responders (as defined by the American College of Rheumatology 20% improvement criteria (ACR20)) negative and 32 responders (ACR70 positive) to infliximab) were studied by surface enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF MS) technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterisation was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by matrix assisted laser desorption/ionisation time-of-flight (MALDI-TOF) MS analysis.
  
  
  RESULTS
  Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity>56%, specificity>77.5%). Moreover, combination of several biomarkers improved the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterised as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4.
  
  
  CONCLUSIONS
  Six plasma biomarkers are characterised, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders.
authors.affiliation: GREPI CNRS UMR 5525, INSERM IFR 130, Université J Fourier, Grenoble, France.
authors.forename: C
authors.initials: C
authors.lastname: Trocmé
authors.forename: H
authors.initials: H
authors.lastname: Marotte
authors.forename: A
authors.initials: A
authors.lastname: Baillet
authors.forename: B
authors.initials: B
authors.lastname: Pallot-Prades
authors.forename: J
authors.initials: J
authors.lastname: Garin
authors.forename: L
authors.initials: L
authors.lastname: Grange
authors.forename: P
authors.initials: P
authors.lastname: Miossec
authors.forename: J
authors.initials: J
authors.lastname: Tebib
authors.forename: F
authors.initials: F
authors.lastname: Berger
authors.forename: M J
authors.initials: MJ
authors.lastname: Nissen
authors.forename: R
authors.initials: R
authors.lastname: Juvin
authors.forename: F
authors.initials: F
authors.lastname: Morel
authors.forename: P
authors.initials: P
authors.lastname: Gaudin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000097:blood*; D011379:Prognosis; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016632:Apolipoprotein A-I; D015415:Biomarkers; D010978:Platelet Factor 4; D000069285:Infliximab