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) , Jean-Philippe Salier (2, 3, 4)

1 Service de Rhumatologie [CHU Rouen]
2 Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques
3 IFRMP 23 - Institut Fédératif de Recherches Multidisciplinaires sur les Peptides
4 Consortium EGERIE

As indicators of responsiveness to a tumour necrosis factor (TNF)alpha 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.

Domaines: Rhumatologie et système ostéo-articulaire; Hématologie; Génétique

Thierry Lequerré, Anne-Christine Gauthier-Jauneau, Carine Bansard, Céline Derambure, Martine Hiron, et al.. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis.. Arthritis Research and Therapy, 2006, 8, pp.R105. ⟨10.1186/ar1990⟩. ⟨inserm-00089669⟩