CHARACTERIZATION OF THE CBIR1 ANTIGENIC RESPONSE FOR DIAGNOSIS AND TREATMENT OF CROHN'S DISEASE
This invention provides methods of diagnosing or predicting susceptibility to Crohn's Disease by determining the presence or absence of genetic variants. In one embodiment, the present invention provides methods to diagnose and/or predict susceptibility to Crohn's Disease in an individual by determining the presence or absence of anti-Cbir1 reactivity and the presence or absence of TLR5 risk variants. In another embodiment, the present invention provides methods to diagnose Crohn's Disease by determining the presence or absence of NFKB1 haplotype H3 and/or ASCA expression. In another embodiment, the present invention provides methods of diagnosing Crohn's Disease by determining the presence or absence of Cbir1 specific peripheral blood T cell proliferation.
1 . A method of diagnosing susceptibility to Crohn's Disease in an individual, comprising:
determining the presence or absence of one or more risk variants at the NFkB locus; and
diagnosing susceptibility to Crohn's Disease based upon the presence of one or more risk variants at the NFkB locus.
2 . The method of claim 1 , wherein the individual is human.
3 . The method of claim 2 , wherein one of the one or more risk variants at the NFkB locus comprises ATA2A03.
4 . The method of claim 1 , wherein one of the one or more risk variants at the NFkB locus comprises SEQ. ID. NO.: 1.
5 . The method of claim 1 , wherein one of the one or more risk variants at the NFkB locus comprises SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12 and SEQ. ID. NO.: 13.
6 . A method of diagnosing Crohn's Disease in an individual, comprising:
determining the presence or absence of NFkB haplotype H3;
determining the presence or absence of ASCA reactivity; and
diagnosing Crohn's Disease based upon the presence of NFkB haplotype H3 and the presence of ASCA reactivity.
7 . The method of claim 6 , wherein the NFkB haplotype H3 comprises SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12 and SEQ. ID. NO.: 13.
8 . A method of diagnosing Crohn's Disease in an individual, comprising:
determining the presence or absence of NFkB haplotype H1;
determining the presence or absence of Cbir1 reactivity; and
diagnosing Crohn's Disease based upon the presence of NFkB haplotype H1 and the presence of Cbir1 reactivity.
9 . The method of claim 8 , wherein the NFkB haplotype H1 comprises SEQ. ID. NO.: 2, SEQ. ID. NO.: 3, SEQ. ID. NO.: 4, SEQ. ID. NO.: 5, SEQ. ID. NO.: 6, SEQ. ID. NO.: 7, SEQ. ID. NO.: 8, SEQ. ID. NO.: 9, SEQ. ID. NO.: 10, SEQ. ID. NO.: 11, SEQ. ID. NO.: 12 and SEQ. ID. NO.: 13.
10 . A method of treating Crohn's Disease in an individual, comprising:
determining the presence or absence of NFkB haplotype H3;
determining the presence or absence of ASCA reactivity; and
treating the Crohn's Disease.
11 . A method of treating Crohn's Disease in an individual, comprising:
determining the presence or absence of NFkB haplotype H1;
determining the presence or absence of Cbir1 reactivity; and
treating the Crohn's Disease.
12 . A method of diagnosing susceptibility to Crohn's Disease in an individual, comprising:
determining the presence or absence of one or more risk variants at the TLR5 locus; and
diagnosing susceptibility to Crohn's Disease based upon the presence of one or more risk variants at the TLR5 locus.
13 . The method of claim 12 , wherein one of the one or more risk variants at the TLR5 locus comprises SEQ. ID. NO.: 15, SEQ. ID. NO.: 16 and/or SEQ. ID. NO.: 17.
14 . A method of diagnosing a Crohn's Disease subtype in an individual, comprising:
determining the presence or absence of an F616L F allele at the TLR5 locus;
determining the presence or absence of an N592S S allele at the TLR5 locus;
determining the presence or absence of OmpC reactivity; and
diagnosing the Crohn's Disease subtype based upon the presence of OmpC reactivity and the presence of the F616L F allele at the TLR5 locus or the N592S S allele at the TLR5 locus.
15 . The method of claim 14 , wherein the F616L F allele at the TLR5 locus comprises SEQ. ID. NO.: 16.
16 . The method of claim 14 , wherein the N592S S allele at the TLR5 locus comprises SEQ. ID. NO.: 15.
17 . The method of claim 14 , wherein the individual is Jewish.
18 . A method of diagnosing a Crohn's Disease subtype in an individual, comprising:
determining the presence or absence of N592S N allele at the TLR5 locus;
determining the presence or absence of Cbir1 reactivity; and
diagnosing the Crohn's Disease subtype based upon the presence of Cbir1 reactivity and the presence of the N592S N allele at the TLR5 locus.
19 . The method of claim 18 , wherein the N592S N allele at the TLR5 locus comprises SEQ. ID. NO.: 15.
20 . The method of claim 18 , wherein the Crohn's Disease subtype comprises internal penetrating phenotype, perianal perforating phenotype and/or severe fibrostenosis phenotype.
21 . A method of treating Crohn's Disease in an individual, comprising:
determining the presence of a high IL-6 production relative to healthy individuals; and
administering a therapeutically effective amount of anti-Cbir1.
22 . A method of diagnosing Crohn's Disease in an individual, comprising:
determining the presence or absence of a high amount of Cbir1-specific IFN-gamma producing cells relative to healthy individuals; and
diagnosing Crohn's Disease based upon the presence of a high amount of Cbir1-specific IFN-gamma producing cells relative to healthy individuals.
23 . A method of diagnosing Crohn's Disease in an individual, comprising:
determining the presence or absence of a high amount of Cbir1-specific peripheral blood T cell proliferation relative to healthy individuals; and
diagnosing Crohn's Disease based upon the presence of a high amount of Cbir1-specific peripheral blood T cell proliferation relative to healthy individuals.