Title:
MUCOSAL GENE SIGNATURES
Document Type and Number:
WIPO Patent Application WO/2009/117791
Kind Code:
A3
Abstract:
Infliximab (IFX) is effective treatment for Crohn's disease (CD) and ulcerative colitis (UC) not responding to standard therapy. 30-40% of patients do not improve and response is often incomplete. The aim of this study is to identify mucosal gene signatures predictive of response to EFX using high-density oligonucleotide arrays. Eight UC patients and 12 CD patients showed healing. In UC, only one probe set was differentially expressed in responders compared with non-responders, ie IL-13Ralpha2. At PAM analysis 2 probe sets, representing IL-13Ralpha2 and IL-I l, separated IBD responders from non-responders with an overall misclassification error rate of 0.046 (2/43), with 100% sensitivity and 91.3 % specificity. The IL-13Ralpha2 probe set was a top-ranked probe set in all our analyses using both LIMMA and PAM strategies. Our gene array studies of mucosal biopsies identified IL-13Ralpha2 in IBD as a predictor of (non-)response to IFX.
Inventors:
RUTGEERTS PAUL (BE)
SCHUIT FRANS (BE)
SCHUIT FRANS (BE)
Application Number:
PCT/BE2009/000021
Publication Date:
April 14, 2011
Filing Date:
March 30, 2009
Export Citation:
Assignee:
UNIV LEUVEN KATH (BE)
RUTGEERTS PAUL (BE)
SCHUIT FRANS (BE)
RUTGEERTS PAUL (BE)
SCHUIT FRANS (BE)
International Classes:
C12Q1/68
Domestic Patent References:
| WO2008028044A2 | 2008-03-06 | |||
| WO2004107240A1 | 2004-12-09 | |||
| WO2007135568A2 | 2007-11-29 |
Foreign References:
| EP1172444A1 | 2002-01-16 |
Other References:
CHARLES P ET AL: "Regulation of cytokines, cytokine inhibitors, and acute-phase proteins following anti-TNF-alpha therapy in rheumatoid arthritis.", JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 1 AUG 1999 LNKD- PUBMED:10415055, vol. 163, no. 3, 1 August 1999 (1999-08-01), pages 1521 - 1528, XP002620410, ISSN: 0022-1767
ARIJS I ET AL: "Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis", GUT, vol. 58, no. 12, December 2009 (2009-12-01), pages 1612 - 1619, XP002620412, ISSN: 0017-5749
ARIJS I ET AL: "Mucosal gene signatures to predict response to infliximab in patients with ulcerative colitis", GUT, vol. 58, no. 12, December 2009 (2009-12-01), pages 1612 - 1619, XP002620412, ISSN: 0017-5749
Attorney, Agent or Firm:
KATHOLIEKE UNIVERSITEIT LEUVEN (Minderbroedersstraat 8A bus 5105, Leuven, BE)
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