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Apolipoprotein A-I and platelet factor 4 are biomarkers for Infliximab response in rheumatoid arthritis
  1. Candice Trocmé (ctrocme{at}chu-grenoble.fr)
  1. GREPI CNRS UMR 5525, INSERM IFR 130, Université J. Fourier, Grenoble / France, France
    1. Hubert Marotte (hubertmarotte{at}aol.com)
    1. Clinic of Rheumatology, Hôpital Edouard Herriot, Lyon / France, France
      1. Athan Baillet (abaillet{at}chu-grenoble.fr)
      1. GREPI CNRS UMR 5525, INSERM IFR 130, Université J. Fourier / Clinic of Rheumatology, Grenoble, France
        1. Béatrice Pallot-Prades (beatrice.pallotprades{at}chu-st-etienne.fr)
        1. Clinic of Rheumatology, CHU Hôpital Bellevue, Saint Etienne / France, France
          1. Jérome Garin (jerome.garin{at}cea.fr)
          1. Protein Chemistry Laboratory, CEA Grenoble / France, France
            1. Laurent Grange (lgrange{at}chu-grenoble.fr)
            1. GREPI CNRS UMR 5525, INSERM IFR 130, Université J. Fourier / Clinic of Rheumatology, Grenoble, France
              1. Pierre Miossec (miossec{at}univ-lyon1.fr)
              1. Clinic of Rheumatology, Hôpital Edouard Herriot, Lyon / France, France
                1. Jacques Tebib (jgtebib{at}wanadoo.fr)
                1. Clinic of Rheumatology, Hôpital Lyon Sud, Lyon / France, France
                  1. François Berger (francois.berger{at}ujf-grenoble.fr)
                  1. INSERM U318, CHU Hôpital Michallon, Grenoble / France, France
                    1. Michael J Nissen (mnissen{at}chu-grenoble.fr)
                    1. Clinic of Rheumatology, CHU Hôpital Sud, Grenoble / France, France
                      1. Robert Juvin (rjuvin{at}chu-grenoble.fr)
                      1. Clinic of Rheumatology, CHU Hôpital Sud, Grenoble / France, France
                        1. Françoise Morel (frmorel.enzymo{at}chu-grenoble.fr)
                        1. GREPI CNRS UMR 5525, INSERM IFR 130, Université J. Fourier, Grenoble / France, Laboratory of Enzymol, France
                          1. Philippe Gaudin (pgaudin{at}chu-grenoble.fr)
                          1. GREPI CNRS UMR 5525, INSERM IFR 130, Université J. Fourier, Grenoble / France, Clinic of Rheumatolog, France

                            Abstract

                            Objectives: The use of biologics 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 RA patients (28 non-responders ACR 20 negative and 32 responders ACR 70 positive to infliximab) were studied by SELDI-TOF-MS technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterization was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by MALDI-TOF 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 both the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterized as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4.

                            Conclusions: We characterized six plasma biomarkers, 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.

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