Biomarker test and method for assessing mucosal healing in response to treatment of ulcerative colitis

Abstract

Mucosal healing is an indication to the disease activity level in patients affected by inflammatory bowel diseases, and it is thus far mainly monitored by endoscopy. Instead or in addition to endoscopy, the invention provides blood test using biomarkers and an index that allows a practitioner to assess the status of mucosal healing, to change or adapt dosage of treatment and to predict which patient will become responder versus non-responder to treatment as assessed by endoscopy. While none of neutrophils cell count, c-reactive protein (CRP), Human type of Cathelicidin (LL-37), or Chitinase 3-like 1 (CHI3L1) alone is able to provide an assessment means of mucosal healing, the invention provides a novel combination of the levels of these biomarkers to assess the level of mucosal healing in relation to endoscopic healing.

What is claimed is: 
     
         1 . A system for non-invasively determining mucosal healing in a human subject undergoing treatment for inflammatory bowel disease using a set of biomarkers, the system comprising:
 a blood sample collection kit for collecting a blood sample from said human subject;   an assay reagent for measuring a concentration of c-reactive protein (CRP) in said blood sample;   a cell count system for producing a cell count of neutrophils in said blood sample;   an assay reagent for measuring a concentration of Human type of Cathelicidin (LL-37) in said blood sample;   an assay reagent for measuring a concentration of Chitinase 3-like 1 (CHI3L1) in said blood sample;   an assay for measuring a concentration of Neutrophil Gelatinase-Associated Lipocalin and Matrix metalloproteinase complex (NGAL-MMP9) in said body specimen; and   a computer system configured to obtain data pertaining to said concentration of CRP, said a cell count of neutrophils, said concentration of LL-37 and said concentration of CHI3L1, and having an interface to produce an output for use by a practitioner assessing mucosal healing in response to treatment, said computer system is configured with program code, when executed, is configured to cause said computer system to:   generate a weighted value of CRP concentration;   generate a weighted value of neutrophils cell count;   generate a weighted value of said LL-37 concentration;   generate a weighted value of CHI3L1 concentration;   generate a weighted value of NGAL-MMP9 concentration;   generate an index value by summing said weighted value of CRP concentration, said weighted value of neutrophils cell count, said weighted value of said LL-37 concentration, said weighted value of CHI3L1 concentration, and said weighted value of NGAL-MMP9 concentration, said index value ranges between zero (0) and a computed maximum value; and   determine that said human subject has a low mucosal healing if said index value is within the upper quarter of said computed maximum value.   
     
     
         2 . A system for non-invasively determining mucosal healing in a human subject undergoing treatment for inflammatory bowel disease using a set of biomarkers, the system comprising:
 a blood sample collection kit for collecting a blood sample from said human subject;   an assay reagent for measuring a concentration of c-reactive protein (CRP) in said blood sample;   an assay reagent for measuring a concentration of Human type of Cathelicidin (LL-37) in said blood sample;   an assay reagent for measuring a concentration of Chitinase 3-like 1 (CHI3L1) in said blood sample;   an assay for measuring a concentration of Neutrophil Gelatinase-Associated Lipocalin and Matrix metalloproteinase complex (NGAL-MMP9) in said body specimen; and   a computer system configured to obtain data pertaining to said concentration of CRP, said a cell count of neutrophils, said concentration of LL-37 and said concentration of CHI3L1, and having an interface to produce an output for use by a practitioner assessing mucosal healing in response to treatment, said computer system is configured with program code, when executed, is configured to cause said computer system to:   generate a weighted value of CRP concentration;   generate a weighted value of neutrophils cell count;   generate a weighted value of said LL-37 concentration;   generate a weighted value of CHI3L1 concentration;   generate a weighted value of NGAL-MMP9 concentration;   generate an index value by summing said weighted value of CRP concentration, said weighted value of said LL-37 concentration, said weighted value of CHI3L1 concentration, and said weighted value of NGAL-MMP9 concentration, said index value ranges between zero (0) and a computed maximum value; and   determine that said human subject has a low mucosal healing if said index value is within the upper quarter of said computed maximum value.