Use of glycans and glycosyltransferases for diagnosing/monitoring inflammatory bowel disease

Abstract

Diagnostic methods for assessing risk of or presence of inflammatory bowel disease in a patient based on glycosyltransferase or histo-blood group antigen signatures or a combination thereof. Also disclosed herein are prognostic methods for monitoring inflammatory bowel disease progression in a patient.

1 . A method for diagnosing and treating inflammatory bowel disease, the method comprising:
 measuring a level of at least one glycosyltransferase in a tissue sample of a subject suspected of having an inflammatory bowel disease (IBD),   determining an expression profile of the least one glycosyltransferase in the tissue sample,   assessing whether the subject has or is at risk for IBD based on the expression profile of the least one glycosyltranferase, and   treating the human subject who is at risk for IBD with an anti-inflammatory agent, an immune suppressant agent, an antibiotic agent, or a combination thereof;   wherein the at least one glycosyltransferase comprises one or more of fucosyltransferase 3 (FUT3), fucosyltranferase 5 (FUT5), or fucosyltransferase 7 (FUT7), ST3 beta-galactoside alpha-2,3-sialyltransferase 3 (ST3Gal III), and ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (ST3 Gal IV).   
     
     
         2 . The method of  claim 1 , wherein the tissue sample is an intestinal sample, a colon biopsy sample, a biofluid sample, a saliva sample, or a stool sample. 
     
     
         3 . The method of  claim 1 , wherein the at least one glycosyltransferase includes ST3Gal IV, and wherein an expression profile representing an elevated level of ST3Gal IV in the tissue sample of the subject as compared with the expression profile of ST3Gal IV in a control tissue sample indicates that the subject has or is at risk for IBD. 
     
     
         4 . The method of  claim 1 , wherein the at least one glycosyltransferase includes one or more of FUT3, FUT5, FUT7, and ST3Gal III; and wherein an expression profile representing a reduced level of the one or more of FUT3, FUT5, FUT7, and ST3Gal III in the tissue sample of the subject as compared with the expression profile of the one or more glycosyltransferases of a control sample indicates that the subject has or is at risk for IBD. 
     
     
         5 . The method of  claim 3 , wherein the at least one glycosyltransferase further includes one or more of FUT3, FUT5, FUT7, and ST3Gal III; and wherein an expression profile representing an elevated level of ST3Gal IV and a reduced level of the one or more FUT3, FUT5, FUT7, and ST3Gal III in the tissue sample of the subject as compared with that in a control tissue sample indicates that the subject has or is at risk for IBD. 
     
     
         6 . The method of  claim 1 , wherein the at least one glycosyltransferase further comprises fucosyltransferase 2 (FUT2) and wherein an expression profile representing an elevated level of ST3Gal IV and a reduced level of the one or more FUT2, FUT3, FUT5, FUT7, and ST3Gal III in the tissue sample of the subject as compared with that in a control tissue sample indicates that the subject has or is at risk for IBD. 
     
     
         7 . The method of  claim 1 , wherein the subject is suspected of having Intestinal Colitis, Ulcerative Colitis, or Crohn's disease. 
     
     
         8 . The method of  claim 1 , wherein the expression level of the at least one glycosyltransferase is determined by measuring the mRNA level of the at least one glycosyltransferase in the tissue sample or by measuring the level of a microRNA that regulates the expression of the at least one glycosyltransferase. 
     
     
         9 . The method of  claim 8 , wherein the mRNA and microRNA levels are measured by PCR, in situ hybridization, RNA sequencing, or flow cytometry. 
     
     
         10 . A method for diagnosing and treating Ulcerative Colitis, the method comprising:
 measuring the level of fucosyltransferase 2 (FUT2) in a tissue sample of a subject suspected of having Ulcerative Colitis (UC),   assessing whether the subject has or is at risk for UC based on the expression level of FUT2, wherein an expression level representing a reduced level of FUT2 in the tissue sample of the subject as compared with that in a control tissue sample indicates that the subject has or is at risk for UC, and   treating the human subject who is at risk for UC with an anti-inflammatory agent, an immune suppressant agent, an antibiotic agent, or a combination thereof.   
     
     
         11 . The method of  claim 10 , wherein the tissue sample is an intestinal sample, a colon biopsy sample, a biofluid sample, a saliva sample, or a stool sample. 
     
     
         12 . The method of  claim 10 , wherein the expression level of FUT2 is the mRNA level of FUT2 or the level of a microRNA that regulates FUT2 expression. 
     
     
         13 . The method of  claim 12 , wherein the mRNA and microRNA levels are measured by PCR, in situ hybridization, RNA sequencing, or flow cytometry. 
     
     
         14 - 19 . (canceled) 
     
     
         21 . A method for monitoring and treating inflammatory bowel disease progression, the method comprising:
 measuring a first expression level of at least one glycosyltransferase in a first tissue sample obtained from a subject having inflammatory bowel disease (IBD) at a first time point and a second expression level of the at least one glycosyltransferase in a second tissue sample obtained from the subject at a second time point, which is later than the first time point;   determining a first expression profile of the at least one glycosyltransferase in the first tissue sample and a second expression profile of the at least one glycosyltransferase in the second tissue sample; and   assessing IBD progress in the subject based on the second expression profile as compared with the first expression profile, wherein a change between the first expression profile and the second expression profile is indicative of IBD progression or regression in the subject; and   treating the subject who shows IBD progression with an anti-inflammatory agent, an immune suppressant agent, an antibiotic agent, or a combination thereof;   wherein the at least one glycosyltransferase comprises one or more of fucosyltransferase 3 (FUT3), fucosyltranferase 5 (FUT5), or fucosyltransferase 7 (FUT7), ST3 beta-galactoside alpha-2,3-sialyltransferase 3 (ST3Gal III), and ST3 beta-galactoside alpha-2,3-sialyltransferase 4 (ST3 Gal IV).   
     
     
         22 . The method of  claim 21 , wherein the first and second tissue samples are both intestinal samples, colon biopsy samples, biofluid samples, saliva samples, or stool samples. 
     
     
         23 . The method of  claim 21 , wherein the at least one glycosyltransferase includes ST3Gal IV, and wherein the second expression profile representing an elevated level of ST3Gal IV as compared with the first expression profile indicates disease progression in the subject and the second expression profile representing a reduced level of ST3Gal IV as compared with the second expression profile indicates disease regression in the subject. 
     
     
         24 . The method of  claim 21 , wherein the at least one glycosyltransferase includes one or more of FUT3, FUT5, FUT7, and ST3Gal III; and wherein the second expression profile representing a reduced level of the one or more of FUT3, FUT5, FUT7, and ST3Gal III as compared with the first expression profile indicates IBD progression in the subject and the second expression profile representing an elevated level of the one or more of FUT3, FUT5, FUT7, and ST3Gal III as compared with the first expression profile indicates IBD regression in the subject. 
     
     
         25 . The method of  claim 21 , wherein the at least one glycosyltransferase further includes FUT2, wherein the second expression profile representing an elevated level of ST3Gal IV and a reduced level of the one or more FUT2, FUT3, FUT5, FUT7, and ST3Gal III as compared with the first expression profile indicates IBD progression in the subject, and wherein the second expression profile representing a reduced level of ST3Gal IV and an elevated level of the one or more FUT2, FUT3, FUT5, FUT7, and ST3Gal III as compared with the first expression profile indicates IBD regression in the subject. 
     
     
         26 . The method of  claim 21 , wherein the subject is suspected of having Intestinal Colitis, Ulcerative Colitis, or Crohn's disease. 
     
     
         27 . The method of  claim 21 , wherein the first and second expression levels of the at least one glycosyltransferase are the mRNA level of the at least one glycosyltransferase or the level of one or more microRNAs that regulate expression of the at least one glycosyltransferase. 
     
     
         28 . The method of  claim 27 , wherein the mRNA and microRNA levels are measured by PCR, in situ hybridization, RNA sequencing, or flow cytometry. 
     
     
         29 . The method of  claim 21 , wherein the subject has undergone a treatment of IBD; wherein either the first and second tissue samples are obtained before and after the treatment, respectively, or at least one of the samples is obtained during the course of the treatment; and wherein the method further comprises assessing the efficacy of the treatment based on the second expression profile as compared with the first expression profile. 
     
     
         30 . The An in vitro method of  claim 21 ,
 wherein the at least one glycosyltransferase is fucosyltransferase 2 (FUT2), and wherein the IBD is Ulcerative Colitis.   
     
     
         31 - 41 . (canceled)