Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis
- C Trocmé1,2,
- H Marotte3,
- A Baillet1,5,
- B Pallot-Prades4,
- J Garin6,
- L Grange1,5,
- P Miossec3,
- J Tebib7,
- F Berger8,
- M J Nissen5,
- R Juvin5,
- F Morel1,2,
- P Gaudin1,5
- 1GREPI CNRS UMR 5525, INSERM IFR 130, Université J Fourier, Grenoble, France
- 2Laboratory of Enzymology/DBPC, CHU Hôpital Michallon, Grenoble, France
- 3Clinic of Rheumatology, Hôpital Edouard Herriot, Lyon, France
- 4Clinic of Rheumatology, CHU Hôpital Bellevue, Saint Etienne, France
- 5Clinic of Rheumatology, CHU Hôpital Sud, Grenoble, France
- 6Protein Chemistry Laboratory, CEA Grenoble, France
- 7Clinic of Rheumatology, Hôpital Lyon Sud, Lyon, France
- 8INSERM U318, CHU Hôpital Michallon, Grenoble, France
- Professor P Gaudin, Clinic of Rheumatology/GREPI TIMC-Imag UMR CNRS 5525, CHU Hôpital Sud, Avenue de Kimberley, BP 338, 38434 Echirolles Cedex, France;
- Accepted 13 July 2008
- Published Online First 29 July 2008
Objectives: 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.
Competing interests: None declared.
Funding: This work was supported by grants from the “Ministère de l’Enseignement Supérieur et de la Recherche”, the “Région Rhône-Alpes”, Joseph Fourier University, the GEFLUC (department of Grenoble), the “Fondation pour la Recherche Médicale”, the “Direction Régionale de la Recherche Clinique” (CHU Grenoble) and the “Ligue Nationale contre le Cancer”.
Ethics approval: Obtained.
▸ Additional data (Supplementary tables 1 and 2) are published online only at http://ard.bmj.com/content/vol68/issue8