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

被引:123
作者
Lequerre, Thierry
Gauthier-Jauneau, Anne-Christine
Bansard, Carine
Derambure, Celine
Hiron, Martine
Vittecoq, Olivier
Daveau, Maryvonne
Mejjad, Othmane
Daragon, Alain
Tron, Francois
Le Loet, Xavier
Salier, Jean-Philippe [1 ]
机构
[1] INSERM, U519, F-76000 Rouen, France
[2] Hop Rouen, Serv Rhumatol, CHU Rouen, F-76000 Rouen, France
[3] Univ Rouen, Fac Med Pharm, Inst Fed Rech Multidisciplinaire Peptides, F-76000 Rouen, France
[4] Consortium EGERIE, Paris, France
关键词
D O I
10.1186/ar1990
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 reassessed 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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页数:11
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