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Open Access Highly Accessed Research article

Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis

Thierry Lequerré1234, Anne-Christine Gauthier-Jauneau123, Carine Bansard23, Céline Derambure123, Martine Hiron234, Olivier Vittecoq1234, Maryvonne Daveau234, Othmane Mejjad1, Alain Daragon1, François Tron234, Xavier Le Loët1234 and Jean-Philippe Salier234*

Author Affiliations

1 CHU de Rouen, Hôpitaux de Rouen, Service de Rhumatologie, Rouen, F-76000, France

2 Inserm, U519, Rouen, F-76000, France

3 Université Rouen, Faculté de Médecine-Pharmacie, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides, Rouen, F-76000, France

4 Consortium EGERIE, Rouen, Paris, France

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Arthritis Research & Therapy 2006, 8:R105  doi:10.1186/ar1990

Published: 3 July 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.