METHODS FOR DIAGNOSING IRRITABLE BOWEL SYNDROME
The present invention provides methods, systems, and code for accurately classifying whether a sample from an individual is associated with irritable bowel syndrome (IBS). In particular, the present invention is useful for classifying a sample from an individual as an IBS sample using a statistical algorithm and/or empirical data. The present invention is also useful for ruling out one or more diseases or disorders that present with IBS-like symptoms and ruling in IBS using a combination of statistical algorithms and/or empirical data. Thus, the present invention provides an accurate diagnostic prediction of IBS and prognostic information useful for guiding treatment decisions.
1 . A method for classifying whether a sample from an individual is associated with irritable bowel syndrome (IBS), said method comprising:
(a) determining a diagnostic marker profile by detecting the presence or level of at least one diagnostic marker selected from the group consisting of a cytokine, growth factor, anti-neutrophil antibody, anti- Saccharomyces cerevisiae antibody (ASCA), antimicrobial antibody, lactoferrin, anti-tissue transglutaminase (tTG) antibody, lipocalin, matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), alpha-globulin, actin-severing protein, S100 protein, fibrinopeptide, calcitonin gene-related peptide (CGRP), tachykinin, ghrelin, neurotensin, corticotropin-releasing hormone, IBS1, MUC20, VSIG2, CKB, M160, VSIG4, CASP1, NCF4, LYZ, KCNS3, PSME2, MS4A4A, HELLS, COP1, FCGR2A, RFC4, MCM5, TAP2, LRAP, L2DTL and combinations thereof in said sample; and
(b) classifying said sample as an IBS sample or non-IBS sample using an algorithm based upon said diagnostic marker profile.
2 . The method of claim 1 , wherein said cytokine is selected from the group consisting of IL-8, IL-1β, TNF-related weak inducer of apoptosis (TWEAK), leptin, osteoprotegerin (OPG), MIP-3β, GROα, CXCL4/PF-4, CXCL7/NAP-2, and combinations thereof.
3 . The method of claim 1 , wherein said growth factor is selected from the group consisting of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), brain-derived neurotrophic factor (BDNF), amphiregulin (SDGF), and combinations thereof.
4 . The method of claim 1 , wherein said anti-neutrophil antibody is selected from the group consisting of an anti-neutrophil cytoplasmic antibody (ANCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), and combinations thereof.
5 . The method of claim 1 , wherein said ASCA is selected from the group consisting of ASCA-IgA, ASCA-IgG, and combinations thereof.
6 . The method of claim 1 , wherein said antimicrobial antibody is selected from the group consisting of an anti-outer membrane protein C (anti-OmpC) antibody, anti-flagellin antibody, anti-I2 antibody, and combinations thereof.
7 . The method of claim 1 , wherein said lipocalin is selected from the group consisting of neutrophil gelatinase-associated lipocalin (NGAL), an NGAL/MMP-9 complex, and combinations thereof.
8 . The method of claim 1 , wherein said MMP is MMP-9.
9 . The method of claim 1 , wherein said TIMP is TIMP-1.
10 . The method of claim 1 , wherein said alpha-globulin is selected from the group consisting of alpha-2-macroglobulin, haptoglobin, orosomucoid, and combinations thereof.
11 . The method of claim 1 , wherein said actin-severing protein is gelsolin.
12 . The method of claim 1 , wherein said 5100 protein is calgranulin.
13 . The method of claim 1 , wherein said fibrinopeptide is fibrinopeptide A (FIBA).
14 . The method of claim 1 , wherein said diagnostic marker profile is determined by detecting the presence or level of at least two, three, four, five, six, seven, eight, nine, or ten diagnostic markers.
15 . The method of claim 1 , wherein the presence or level of said at least one diagnostic marker is detected using a hybridization assay, amplification-based assay, immunoassay, or immunohistochemical assay.
16 . The method of claim 1 , wherein said method comprises determining said diagnostic marker profile in combination with a symptom profile, wherein said symptom profile is determined by identifying the presence or severity of at least one symptom in said individual; and classifying said sample as an IBS sample or non-IBS sample using an algorithm based upon said diagnostic marker profile and said symptom profile.
17 . The method of claim 16 , wherein said at least one symptom is selected from the group consisting of chest pain, chest discomfort, heartburn, uncomfortable fullness after having a regular-sized meal, inability to finish a regular-sized meal, abdominal pain, abdominal discomfort, constipation, diarrhea, bloating, abdominal distension, negative thoughts or feelings associated with having pain or discomfort, and combinations thereof.
18 . The method of claim 16 , wherein the presence or severity of said at least one symptom is identified using a questionnaire.
19 - 36 . (canceled)
37 . A method for monitoring the progression or regression of irritable bowel syndrome (IBS) in an individual, said method comprising:
(a) determining a diagnostic marker profile by detecting the presence or level of at least one diagnostic marker selected from the group consisting of a cytokine, growth factor, anti-neutrophil antibody, anti- Saccharomyces cerevisiae antibody (ASCA), antimicrobial antibody, lactoferrin, anti-tissue transglutaminase (tTG) antibody, lipocalin, matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), alpha-globulin, actin-severing protein, S100 protein, fibrinopeptide, calcitonin gene-related peptide (CGRP), tachykinin, ghrelin, neurotensin, corticotropin-releasing hormone, IBS1, MUC20, VSIG2, CKB, M160, VSIG4, CASP1, NCF4, LYZ, KCNS3, PSME2, MS4A4A, HELLS, COP1, FCGR2A, RFC4, MCM5, TAP2, LRAP, L2DTL and combinations thereof in a sample from said individual; and
(b) determining the presence or severity of IBS in said individual using an algorithm based upon said diagnostic marker profile.
38 - 47 . (canceled)
48 . A computer-readable medium comprising code for controlling one or more processors to classify whether a sample from an individual is associated with irritable bowel syndrome (IBS), said code comprising:
instructions to apply a statistical process to a data set comprising a diagnostic marker profile to produce a statistically derived decision classifying said sample as an IBS sample or non-IBS sample based upon said diagnostic marker profile,
wherein said diagnostic marker profile indicates the presence or level of at least one diagnostic marker selected from the group consisting of a cytokine, growth factor, anti-neutrophil antibody, anti- Saccharomyces cerevisiae antibody (ASCA), antimicrobial antibody, lactoferrin, anti-tissue transglutaminase (tTG) antibody, lipocalin, matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), alpha-globulin, actin-severing protein, S100 protein, fibrinopeptide, calcitonin gene-related peptide (CGRP), tachykinin, ghrelin, neurotensin, corticotropin-releasing hormone, IBS1, MUC20, VSIG2, CKB, M160, VSIG4, CASP1, NCF4, LYZ, KCNS3, PSME2, MS4A4A, HELLS, COP1, FCGR2A, RFC4, MCM5, TAP2, LRAP, L2DTL and combinations thereof in said sample.
49 - 55 . (canceled)