Antibody to cytolethal distending toxin of campylobacter jejuni

Abstract

The present invention describes methods for preventing IBS, reducing the likelihood of developing IBS and/or treating IBS by administering CDT inhibitors and/or CDT neutralizers to a subject in need thereof. The present invention also describes methods of eliciting a specific immune response and methods of vaccinating a subject to prevent IBS or to reduce the likelihood of developing or having IBS. The present invention further describes methods of diagnosing IBS by detecting the presence or absence of CDT or a CDT marker in a subject.

1 . A method, comprising:
 obtaining a biological sample from a subject selected from the group consisting of: a subject in need of a diagnosis regarding irritable bowel syndrome (IBS), a subject in need of a diagnosis regarding a subset of IBS, a subject in need of a determination of a likelihood of having or developing IBS, a subject in need of a determination of a likelihood of having or developing a subset of IBS, a subject in need of a diagnosis regarding non-ulcer dyspepsia (NUD), a subject in need of a determination regarding small intestinal bacterial overgrowth (SIBO), a subject in need of a determination of a susceptibility to having SIBO, a subject who desires a prognosis of a response to antibiotic treatment for IBS, a subject who desires a prognosis of a response to antibiotic treatment to reduce the likelihood of having IBS and combinations thereof;   detecting the presence or absence of cytolethal distending toxin (CDT) or one or more markers of CDT in the biological sample; and   correlating the presence of CDT or one or more markers of CDT with a likely presence of IBS, a likely presence of a subset of IBS, a likelihood of having or developing IBS, a likelihood of having or developing a subset of IBS a likely presence of NUD, a likely presence of SIBO, a higher susceptibility to having SIBO, a higher likelihood of having a beneficial result from antibiotic treatment for IBS, and/or a higher likelihood of having a beneficial result from antibiotic treatment to reduce the likelihood of having IBS, or   correlating an absence of CDT and an absence of one or more markers of CDT with a likely absence of IBS, a likely absence of the subset of IBS, a lower likelihood of having or developing IBS, a lower likelihood of having or developing the subset of IBS, a likely absence of NUD, a likely absence of SIBO, a lower susceptibility to having SIBO, a lower likelihood of having a beneficial result from antibiotic treatment for IBS, and/or a lower likelihood of having a beneficial result from antibiotic treatment to reduce the likelihood of having IBS.   
     
     
         2 . The method of  claim 1 , further comprising identifying the subject in need of the diagnosis regarding IBS, the subject in need of the diagnosis regarding the subset of IBS, the subject in need of the determination of the likelihood of having or developing IBS, the subject in need of the determination of the likelihood of having or developing subset of IBS, the subject in need of the diagnosis regarding NUD, the subject in need of the determination regarding SIBO, the subject in need of the determination of the susceptibility to having SIBO, the subject who desires the prognosis of the response to antibiotic treatment for IBS, and/or the subject who desires the prognosis of the response to antibiotic treatment to reduce the likelihood of having IBS. 
     
     
         3 . The method of  claim 1 , further comprising choosing an antibiotic therapy for the subject based on the likely presence of IBS, the likely presence of the subset of IBS, the likelihood of having or developing IBS, the likelihood of having or developing the subset of IBS, the likely presence of NUD, the likely presence of SIBO, the higher susceptibility to having SIBO, the higher likelihood of having the beneficial result from antibiotic treatment for IBS, and/or the higher likelihood of having the beneficial result from antibiotic treatment to reduce the likelihood of having IBS. 
     
     
         4 . The method of  claim 1 , wherein the subset of IBS is selected from the group consisting of constipation-predominant IBS, diarrhea-predominant IBS, mixed IBS, undetermined IBS, and antibiotic responsive IBS. 
     
     
         5 . The method of  claim 1 , wherein the one or more markers of CDT is an antibody capable of binding specifically to CDT, CdtA, CdtB, CdtC or a fragment thereof. 
     
     
         6 . The method of  claim 5 , wherein the CdtB is CdtB of  Campylobacter jejuni.    
     
     
         7 . The method of  claim 6 , wherein the CdtB of  Campylobacter jejuni  has an amino acid sequence at least 80% identical to SEQ ID NO:5. 
     
     
         8 . The method of  claim 7 , wherein the antibody is capable of binding specifically to an epitope on 5 to 22 contiguous residues of SEQ ID NO:5. 
     
     
         9 . The method of  claim 8 , wherein the epitope is on 17 contiguous residues as disclosed by SEQ ID NO:3. 
     
     
         10 . The method of  claim 5 , wherein the antibody is capable of binding specifically to an epitope on SEQ ID NO:4. 
     
     
         11 . The method of  claim 5 , wherein the CdtB is CdtB of  Campylobacter coli  and has an amino acid sequence at least 80% identical to SEQ ID NO:1. 
     
     
         12 . The method of  claim 5 , wherein the CdtB is CdtB of  Escherichia coli, Salmonella, Shigella , or  Clostridium difficile.    
     
     
         13 . A method, comprising:
 providing a composition to elicit a specific immune response, comprising: an agent selected from the group consisting of a fragment of cytolethal distending toxin (CDT) incapable of causing irritable bowel syndrome (IBS), CdtA incapable of causing IBS, CdtB incapable of causing IBS, CdtC incapable of causing IBS, CDT mutein incapable of causing IBS, a fragment of CDT mutein incapable of causing IBS, CdtA mutein incapable of causing IBS, CdtB mutein incapable of causing IBS, CdtC mutein incapable of causing IBS, a bacterium comprising a mutated CDT gene rendering the bacterium incapable of causing IBS, and combinations thereof; and   administering the composition to a subject in need thereof to elicit a specific immune response.   
     
     
         14 . The method of  claim 13 , wherein eliciting the specific immune response reduces the subject's likelihood of developing or having IBS, or reduces the subject's likelihood of developing or having non-ulcer dyspepsia (NUD). 
     
     
         15 . The method of  claim 13 , wherein the bacterium is  Campylobacter jejuni  81-176 that failed to express a functional cytolethal distending toxin B (CdtB) due to an insertion mutation at the gene for CdtB. 
     
     
         16 . The method of  claim 13 , wherein the bacterium is killed. 
     
     
         17 . The method of  claim 13 , wherein the bacterium is attenuated. 
     
     
         18 . A method, comprising:
 providing a cytolethal distending toxin (CDT) inhibitor and/or a CDT neutralizer to reduce the likelihood of developing or having irritable bowel syndrome (IBS) or to reduce the likelihood of developing or having non-ulcer dyspepsia (NUD); and   administering the CDT inhibitor and/or the CDT neutralizer to a subject in need thereof.   
     
     
         19 . The method of  claim 18 , wherein the CDT inhibitor and/or the CDT neutralizer is an antibody capable of binding specifically to CDT or a subunit of CDT. 
     
     
         20 . The method of  claim 19 , wherein the subunit of CDT is CdtB. 
     
     
         21 - 35 . (canceled)