Methods of assessing crohn's disease patient phenotype by i2, ompc and asca serologic response

Abstract

The invention provides a method of diagnosing or predicting susceptibility to a clinical subtype of Crohn's disease in a subject having Crohn's disease by determining the presence or absence of IgA anti-I2 antibodies in the subject, where the presence of the IgA anti-I2 antibodies indicates that the subject has a clinical subtype of Crohn's disease. In one embodiment, a method of the invention is practiced by further determining the presence or absence in the subject of a NOD2 variant, anti- Saccharomyces cerevisiae antibodies (ASCA), IgA anti-OmpC antibodies, or perinuclear anti-neutrophil cytoplasmic antibodies (pANCA). The methods of the invention can be used to diagnose or predict susceptibility to a clinical subtype of Crohn's disease, for example, a fibrostenotic subtype, a subtype characterized by the need for small bowel surgery, or a subtype characterized by the absence of features of ulcerative colitis.

1 - 29 . (canceled) 
     
     
         30 . A method for determining a risk of having or developing a clinical subtype of Crohn's disease characterized by internal perforating disease in a subject with Crohn's disease, the method comprising:
 (a) contacting a sample obtained from said subject with an antigen specifically reactive with IgA anti-OmpC antibodies; and   (b) determining the presence and magnitude of IgA anti-OmpC antibody response in said sample by detecting specific binding of said IgA anti-OmpC antibodies to said antigen, wherein a greater magnitude of IgA anti-OmpC antibody response is indicative of a greater risk of said subject having or developing said clinical subtype of Crohn's disease characterized by internal perforating disease.   
     
     
         31 . The method of  claim 30 , wherein said sample is whole blood, plasma, saliva, or serum. 
     
     
         32 . The method of  claim 30 , further comprising determining the presence and magnitude of IgA anti-I2 antibodies, anti- Saccharomyces cerevisiae  antibodies (ASCA), or a combination thereof. 
     
     
         33 . The method of  claim 30 , wherein the presence and magnitude of said IgA anti-OmpC antibody response is determined with an enzyme linked immunosorbent assay (ELISA). 
     
     
         34 . The method of  claim 30 , wherein said antigen comprises an OmpC antigen. 
     
     
         35 . The method of  claim 30 , further comprising determining the presence or absence of a NOD2 variant. 
     
     
         36 . The method of  claim 35 , wherein said NOD2 variant is selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.