Development and Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome in Human Subjects
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{"title"=>"Development and validation of a biomarker for diarrhea-predominant irritable bowel syndrome in human subjects", "type"=>"journal", "authors"=>[{"first_name"=>"Mark", "last_name"=>"Pimentel", "scopus_author_id"=>"7006799213"}, {"first_name"=>"Walter", "last_name"=>"Morales", "scopus_author_id"=>"57117524600"}, {"first_name"=>"Ali", "last_name"=>"Rezaie", "scopus_author_id"=>"10044809800"}, {"first_name"=>"Emily", "last_name"=>"Marsh", "scopus_author_id"=>"56430602400"}, {"first_name"=>"Anthony", "last_name"=>"Lembo", "scopus_author_id"=>"26426421700"}, {"first_name"=>"James", "last_name"=>"Mirocha", "scopus_author_id"=>"6603117339"}, {"first_name"=>"Daniel A.", "last_name"=>"Leffler", "scopus_author_id"=>"6603048126"}, {"first_name"=>"Zachary", "last_name"=>"Marsh", "scopus_author_id"=>"49461306300"}, {"first_name"=>"Stacy", "last_name"=>"Weitsman", "scopus_author_id"=>"56705105600"}, {"first_name"=>"Kathleen S.", "last_name"=>"Chua", "scopus_author_id"=>"49461081100"}, {"first_name"=>"Gillian M.", "last_name"=>"Barlow", "scopus_author_id"=>"55300614800"}, {"first_name"=>"Enoch", "last_name"=>"Bortey", "scopus_author_id"=>"6506150607"}, {"first_name"=>"William", "last_name"=>"Forbes", "scopus_author_id"=>"35510425900"}, {"first_name"=>"Allen", "last_name"=>"Yu", "scopus_author_id"=>"56643826100"}, {"first_name"=>"Christopher", "last_name"=>"Chang", "scopus_author_id"=>"57201578519"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0126438", "issn"=>"19326203", "sgr"=>"84929340217", "pui"=>"604377953", "scopus"=>"2-s2.0-84929340217", "pmid"=>"25970536"}, "id"=>"24c24db9-fddf-33f1-b88c-96f59c704076", "abstract"=>"Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding \"organic\" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density>/=2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD>/=1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.", "link"=>"http://www.mendeley.com/research/development-validation-biomarker-diarrheapredominant-irritable-bowel-syndrome-human-subjects-1", "reader_count"=>75, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>7, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>7, "Other"=>10, "Student > Master"=>11, "Student > Bachelor"=>5, "Lecturer"=>4, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Researcher"=>17, "Student > Doctoral Student"=>7, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2066672", "https://ndownloader.figshare.com/files/2066674", "https://ndownloader.figshare.com/files/2066675", "https://ndownloader.figshare.com/files/2066676", "https://ndownloader.figshare.com/files/2066677", "https://ndownloader.figshare.com/files/2066679", "https://ndownloader.figshare.com/files/2066680"], "description"=>"<div><p>Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding “organic” conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.</p></div>", "links"=>[], "tags"=>["od", "subject", "host antibodies", "Rome criteria", "histologic confirmation", "antibody", "bowel syndrome", "host gut", "plasma levels", "elisa", "likelihood ratio", "auc", "ibd", "65 years", "ibs", "Cytolethal distending toxin B", "bowel disease"], "article_id"=>1413830, "categories"=>["Biological Sciences"], "users"=>["Mark Pimentel", "Walter Morales", "Ali Rezaie", "Emily Marsh", "Anthony Lembo", "James Mirocha", "Daniel A. Leffler", "Zachary Marsh", "Stacy Weitsman", "Kathleen S. Chua", "Gillian M. Barlow", "Enoch Bortey", "William Forbes", "Allen Yu", "Christopher Chang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0126438.s001", "https://dx.doi.org/10.1371/journal.pone.0126438.s002", "https://dx.doi.org/10.1371/journal.pone.0126438.s003", "https://dx.doi.org/10.1371/journal.pone.0126438.s004", "https://dx.doi.org/10.1371/journal.pone.0126438.s005", "https://dx.doi.org/10.1371/journal.pone.0126438.s006", "https://dx.doi.org/10.1371/journal.pone.0126438.s007"], "stats"=>{"downloads"=>6, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Development_and_Validation_of_a_Biomarker_for_Diarrhea_Predominant_Irritable_Bowel_Syndrome_in_Human_Subjects_/1413830", "title"=>"Development and Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome in Human Subjects", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-05-13 04:10:40"}
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  • {"files"=>["https://ndownloader.figshare.com/files/2066657"], "description"=>"<p>Titers were higher in IBS subjects when compared to any other group (<i>P</i><0.001). Dots represent outlier subjects beyond the whisker plot.</p>", "links"=>[], "tags"=>["od", "subject", "host antibodies", "Rome criteria", "histologic confirmation", "antibody", "bowel syndrome", "host gut", "plasma levels", "elisa", "likelihood ratio", "auc", "ibd", "65 years", "ibs", "Cytolethal distending toxin B", "bowel disease"], "article_id"=>1413816, "categories"=>["Biological Sciences"], "users"=>["Mark Pimentel", "Walter Morales", "Ali Rezaie", "Emily Marsh", "Anthony Lembo", "James Mirocha", "Daniel A. Leffler", "Zachary Marsh", "Stacy Weitsman", "Kathleen S. Chua", "Gillian M. Barlow", "Enoch Bortey", "William Forbes", "Allen Yu", "Christopher Chang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0126438.g002", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_optical_density_OD_for_the_anti_vinculin_antibody_among_the_groups_/1413816", "title"=>"Comparison of optical density (OD) for the anti-vinculin antibody among the groups.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-13 04:10:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/2066658"], "description"=>"<p>CI, confidence interval.</p>", "links"=>[], "tags"=>["od", "subject", "host antibodies", "Rome criteria", "histologic confirmation", "antibody", "bowel syndrome", "host gut", "plasma levels", "elisa", "likelihood ratio", "auc", "ibd", "65 years", "ibs", "Cytolethal distending toxin B", "bowel disease"], "article_id"=>1413817, "categories"=>["Biological Sciences"], "users"=>["Mark Pimentel", "Walter Morales", "Ali Rezaie", "Emily Marsh", "Anthony Lembo", "James Mirocha", "Daniel A. Leffler", "Zachary Marsh", "Stacy Weitsman", "Kathleen S. Chua", "Gillian M. Barlow", "Enoch Bortey", "William Forbes", "Allen Yu", "Christopher Chang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0126438.g003", "stats"=>{"downloads"=>1, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Receiver_operator_curve_ROC_comparing_anti_CdtB_and_anti_vinculin_levels_in_D_IBS_subjects_and_IBD_subjects_/1413817", "title"=>"Receiver operator curve (ROC) comparing anti-CdtB and anti-vinculin levels in D-IBS subjects and IBD subjects.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-05-13 04:10:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/2066659"], "description"=>"<p><sup>a</sup>Values are given as mean ± standard deviation</p><p><sup>b</sup> Crohn’s disease</p><p><sup>c</sup> ulcerative colitis</p><p>Patient demographics.</p>", "links"=>[], "tags"=>["od", "subject", "host antibodies", "Rome criteria", "histologic confirmation", "antibody", "bowel syndrome", "host gut", "plasma levels", "elisa", "likelihood ratio", "auc", "ibd", "65 years", "ibs", "Cytolethal distending toxin B", "bowel disease"], "article_id"=>1413818, "categories"=>["Biological Sciences"], "users"=>["Mark Pimentel", "Walter Morales", "Ali Rezaie", "Emily Marsh", "Anthony Lembo", "James Mirocha", "Daniel A. Leffler", "Zachary Marsh", "Stacy Weitsman", "Kathleen S. Chua", "Gillian M. Barlow", "Enoch Bortey", "William Forbes", "Allen Yu", "Christopher Chang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0126438.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_demographics_/1413818", "title"=>"Patient demographics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-13 04:10:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/2066660"], "description"=>"<p><sup>a</sup> positive likelihood ratio</p><p><sup>b</sup> negative likelihood ratio</p><p>Cutoffs for anti-CdtB and anti-vinculin for the diagnosis of D-IBS vs. IBD.</p>", "links"=>[], "tags"=>["od", "subject", "host antibodies", "Rome criteria", "histologic confirmation", "antibody", "bowel syndrome", "host gut", "plasma levels", "elisa", "likelihood ratio", "auc", "ibd", "65 years", "ibs", "Cytolethal distending toxin B", "bowel disease"], "article_id"=>1413819, "categories"=>["Biological Sciences"], "users"=>["Mark Pimentel", "Walter Morales", "Ali Rezaie", "Emily Marsh", "Anthony Lembo", "James Mirocha", "Daniel A. Leffler", "Zachary Marsh", "Stacy Weitsman", "Kathleen S. Chua", "Gillian M. Barlow", "Enoch Bortey", "William Forbes", "Allen Yu", "Christopher Chang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0126438.t002", "stats"=>{"downloads"=>8, "page_views"=>77, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cutoffs_for_anti_CdtB_and_anti_vinculin_for_the_diagnosis_of_D_IBS_vs_IBD_/1413819", "title"=>"Cutoffs for anti-CdtB and anti-vinculin for the diagnosis of D-IBS vs. IBD.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-05-13 04:10:40"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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