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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
 
Arthritis Res Ther. 2006; 8(4): R105.
Published online Jul 3, 2006. doi:  10.1186/ar1990
PMCID: PMC1779405
Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis
Thierry Lequerré,1,2,3,4 Anne-Christine Gauthier-Jauneau,1,2,3 Carine Bansard,2,3 Céline Derambure,1,2,3 Martine Hiron,2,3,4 Olivier Vittecoq,1,2,3,4 Maryvonne Daveau,2,3,4 Othmane Mejjad,1 Alain Daragon,1 François Tron,2,3,4 Xavier Le Loët,1,2,3,4 and Jean-Philippe Saliercorresponding author2,3,4
1CHU de Rouen, Hôpitaux de Rouen, Service de Rhumatologie, Rouen, F-76000, France
2Inserm, U519, Rouen, F-76000, France
3Université Rouen, Faculté de Médecine-Pharmacie, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Rouen, F-76000, France
4Consortium EGERIE, Rouen, Paris, France
corresponding authorCorresponding author.
Thierry Lequerré: thierry.lequerre/at/univ-rouen.fr; Anne-Christine Gauthier-Jauneau: anne-christine.jauneau/at/univ-rouen.fr; Carine Bansard: carine.bansard/at/univ-rouen.fr; Céline Derambure: celine.derambure/at/univ-rouen.fr; Martine Hiron: Martine.Hiron/at/univ-rouen.fr; Olivier Vittecoq: Olivier.Vittecoq/at/chu-rouen.fr; Maryvonne Daveau: Maryvonne.Daveau/at/univ-rouen.fr; Othmane Mejjad: othmane.mejjad/at/chu-rouen.fr; Alain Daragon: alain.daragon/at/chu-rouen.fr; François Tron: francois.tron/at/chu-rouen.fr; Xavier Le Loët: xavier.le-loet/at/chu-rouen.fr; Jean-Philippe Salier: Jean-Philippe.Salier/at/univ-rouen.fr
Received March 28, 2006; Revisions requested May 16, 2006; Revised May 23, 2006; Accepted July 8, 2006.
Abstract
As indicators of responsiveness to a tumour necrosis factor (TNF)α blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination.
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