Methods of using genetic variants for the diagnosis and treatment of inflammatory bowel disease
This invention provides methods of diagnosis, predicting and diagnosing susceptibility to, predicting disease progression and treatment of inflammatory bowel disease (IBD), including Crohn's disease and/or subtypes of Crohn's disease (CD) and/or Ulcerative Colitis (UC). In one embodiment, a method of the invention is practiced by determining the presence or absence of the genetic variants NOD2, TLR8, TLR2, CARD8, CARD15 and/or JAK3 to diagnose, predict and diagnose susceptibility and predict disease progression in an individual. In another embodiment, a method of the invention is practiced by determining the presence or absence of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and/or pANCA in an individual. In another embodiment, the invention further associates the presence or absence of the risk variants with the expression of anti-Cbir1, anti-OmpC, ASCA, anti-I2 and/or pANCA for the diagnosis, prediction of susceptibility, prediction of disease progression and/or treatment of IBD, including CD and/or UC.
1. A method of treating inflammatory bowel disease in a subject, comprising:
(a) providing a sample from a subject;
(b) determining whether the subject has Inflammatory Bowel Disease (IBD) or is susceptible to developing the IBD, by:
(i) assaying the sample to detect an expression of two or more genes, each independently comprising a nucleic acid sequence provided in SEQ ID NOs: 18, 19, or 20;
(ii) assaying the sample to detect an expression of a serological marker comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA or anti-I2; and
(iii) detecting the expression of the two or more genes and the expression of the serological marker; and
(c) treating the IBD in the subject.
2. The method of claim 1 , wherein the IBD comprises Crohn's disease (CD) or ulcerative colitis (UC).
3. The method of claim 1 , wherein assaying the sample to detect the serological marker in (ii) comprises performing Northern blot, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-P AGE), Western Blot, mass spectrometric analysis, or a combination thereof.
4. The method of claim 1 , wherein assaying the sample to detect the two or more genes of (i) comprises performing an allelic discrimination assay, sequence analysis, allele-specific oligonucleotide hybridization assay, heteroplex mobility assay (HMA), single strand conformational polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), or a combination thereof.
5. The method of claim 1 , further comprising comparing a level of expression of the serological marker to a level of expression of the serological marker in a normal subject.
6. The method of claim 1 , wherein the subject is a pediatric subject.
7. The method of claim 2 , wherein the IBD is CD.
8. The method of claim 1 , further comprising detecting the expression of two or more serological markers comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA, or anti-I2, or a combination thereof.
9. The method of claim 1 , further comprising detecting the expression of three or more serological markers comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA, or anti-I2, or a combination thereof.
10. The method of claim 1 , further comprising detecting the expression of four or more serological markers comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA, or anti-I2, or a combination thereof.
11. The method of claim 5 , wherein the level of expression of the serological marker that is detected in (iii) is high relative to a level of the serological marker in the normal individual.
12. The method of claim 1 , wherein the two or more genes comprise (i) a first gene comprising a nucleic acid sequence provided in SEQ ID NO: 18, (ii) a second gene comprising a nucleic acid sequence provided in SEQ ID NO: 19, and (iii) a third gene comprising a nucleic acid sequence provided in SEQ ID NO: 20.
13. The method of claim 1 , further comprising detecting the expression of three genes, each independently comprising a nucleic acid sequence provided in SEQ ID NOS: 18, 19, and 20, and the expression of serological markers comprising anti-Cbir1 antibody, pANCA, and ASCA.
14. The method of claim 1 , further comprising detecting the expression of three genes, each independently comprising a nucleic acid sequence provided in SEQ ID NOS: 18, 19, and 20, and the expression of serological markers comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA, and anti-I2.
15. The method of claim 2 , wherein the CD is a subtype of CD comprising an aggressive complicating phenotype, a small bowel disease phenotype, an internal penetrating disease phenotype, fibrostenosing disease phenotype, or a combination thereof.
16. The method of claim 1 , wherein treating the IBD in (c) comprises administering to the subject a therapeutic agent.
17. A method of treating inflammatory bowel disease (IBD) in a subject comprising administering to the subject a therapeutically effective amount of a therapeutic agent, provided a presence of two or more genes comprising a nucleic acid sequence provided in any two of SEQ ID NOS: 18, 19, and 20, and an expression of one or more serological markers comprising anti-Cbir1 antibody, pANCA, anti-OmpC, ASCA, or anti-I2, or a combination thereof, are detected in a sample obtained from the subject.
18. The method of claim 17 , wherein the IBD is Crohn's disease.
19. The method of claim 17 , wherein the two or more genes comprise (i) a first gene comprising a nucleic acid sequence provided in SEQ ID NO: 18, (ii) a second gene comprising a nucleic acid sequence provided in SEQ ID NO: 19, and (iii) a third gene comprising a nucleic acid sequence provided in SEQ ID NO: 20.
20. The method of claim 19 , wherein the one or more serological markers comprises anti-Cbir1 antibody, pANCA, and ASCA.