Mo1566 ANTI-VINCULIN AND ANTI-CYTOLETHAL DISTENDING TOXIN B (CDTB) ANTIBODIES ARE LINKED DIRECTLY TO CHANGES IN THE MICROBIOME AND CYTOKINE EXPRESSION AS PART OF THE PATHOPHYSIOLOGY OF POST-INFECTIOUS IBS

2020 ◽  
Vol 158 (6) ◽  
pp. S-898
Author(s):  
Gabriela Leite ◽  
Walter Morales ◽  
Gonzalo Parodi ◽  
Stacy Weitsman ◽  
Shreya Celly ◽  
...  
Keyword(s):  
Cytokine Expression ◽  
Cytolethal Distending Toxin ◽  
Toxin B ◽  
Post Infectious

scholarly journals Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 303
Author(s):  
Maysaa El Sayed Zaki ◽  
Dina Elhammady ◽  
Mona Foda Salama ◽  
Mostafa Abdelsalam ◽  
Asmaa Osama Bakr Osman
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastrointestinal Disorder ◽  
The Other ◽  
University Hospital ◽  
Cytolethal Distending Toxin ◽  
Retrospective Case ◽  
Toxin B ◽  
Control Subjects ◽  
Irritable Bowel ◽  
Post Infectious

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility. Objective: This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control. Subjects and methods: This retrospective case-control study was conducted on 100 patients with IBS, as determined by a questionnaire based on Rome IV criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020. Results: Anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496ng/ml, 2.47±0.60ng/ml)  when compared to control subjects (1.13±0.249ng/ml, 2.1±0.24 ng/ml), respectively with P=0.001 for both.  Anti-vinculin level was significantly higher in the IBS-D subtype than the other subtypes (P=0.001) while, Anti-CdtB was significantly elevated in IBS-C, IBS-D subgroups compared to control subjects (P=0.001). Conclusion: Findings of the present study support the hypothesis that IBS results from post-infectious disorders initiated by bacterial enteritis. A hypothesis could be applied to all IBS subgroups. On the other hand. These biomarkers might reflect the post-infectious state's severity. These findings need further extensive longitudinal studies in patients with IBS.

scholarly journals Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 303
Author(s):  
Maysaa El Sayed Zaki ◽  
Dina Elhammady ◽  
Mona Foda Salama ◽  
Mostafa Abdelsalam ◽  
Asmaa Osama Bakr Osman
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastrointestinal Disorder ◽  
The Other ◽  
University Hospital ◽  
Cytolethal Distending Toxin ◽  
Retrospective Case ◽  
Toxin B ◽  
Control Subjects ◽  
Irritable Bowel ◽  
Post Infectious

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility. Objective: This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control. Subjects and methods: This retrospective case-control study was conducted on 100 subjects with IBS, as determined by a questionnaire based on Rome IV criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020. Results: Anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496ng/ml, 2.47±0.60ng/ml)  when compared to control subjects (1.13±0.249ng/ml, 2.1±0.24 ng/ml), respectively with P=0.001 for both.  Anti-vinculin level was significantly higher in the IBS-D subtype than the other subtypes (P=0.001) while, Anti-CdtB was significantly elevated in IBS-C, IBS-D subgroups compared to control subjects (P=0.001). Conclusion: Findings of the present study support the hypothesis that IBS results from post-infectious disorders initiated by bacterial enteritis. A hypothesis could be applied to all IBS subgroups. On the other hand. These biomarkers might reflect the post-infectious state's severity. These findings need further extensive longitudinal studies in patients with IBS.

scholarly journals Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 303
Author(s):  
Maysaa El Sayed Zaki ◽  
Dina Elhammady ◽  
Mona Foda Salama ◽  
Mostafa Abdelsalam ◽  
Asmaa Osama Bakr Osman
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastrointestinal Disorder ◽  
The Other ◽  
University Hospital ◽  
Cytolethal Distending Toxin ◽  
Retrospective Case ◽  
Toxin B ◽  
Control Subjects ◽  
Irritable Bowel ◽  
Post Infectious

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility. Objective: This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control. Subjects and methods: This retrospective case-control study was conducted on 100 subjects with IBS, as determined by a questionnaire based on Rome III criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020. Results: Anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496, 2.47±0.60)  when compared to control subjects (1.13±0.249ng/ml, 2.1±0.24 ng/ml), respectively with P=0.001 for both.  Anti-vinculin level was significantly higher in the IBS-D subtype than the other subtypes (P=0.001) while, Anti-CdtB was significantly elevated in IBS-C, IBS-D subgroups compared to control subjects (P=0.001). Conclusion: Findings of the present study support the hypothesis that IBS results from post-infectious disorders initiated by bacterial enteritis. A hypothesis could be applied to all IBS subgroups. On the other hand. These biomarkers might reflect the post-infectious state's severity.

scholarly journals Study of Antibodies to Cytolethal Distending Toxin B (CdtB) and Antibodies to Vinculin in Patients with Irritable Bowel Syndrome

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 303
Author(s):  
Maysaa El Sayed Zaki ◽  
Dina Elhammady ◽  
Mona Foda Salama ◽  
Mostafa Abdelsalam ◽  
Asmaa Osama Bakr Osman
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastrointestinal Disorder ◽  
The Other ◽  
University Hospital ◽  
Cytolethal Distending Toxin ◽  
Retrospective Case ◽  
Toxin B ◽  
Control Subjects ◽  
Irritable Bowel ◽  
Post Infectious

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, categorized into various subtypes. Post-infection IBS may be attributed to the release of cytolethal distending toxin B (CdtB), which cross-reacts with the adhesion protein vinculin responsible for normal intestinal contractility. Objective: This study aims to identify anti-CdtB and anti-vinculin levels in IBS patients compared to healthy control. Subjects and methods: This retrospective case-control study was conducted on 100 subjects with IBS, as determined by a questionnaire based on Rome III criteria, recruited from the outpatient clinics of the Tropical Medicine at Mansoura University Hospital from January 2019 to January 2020. Results: The optical density (OD) results of the anti-vinculin and anti-CdtB levels were significantly elevated in patients with IBS (1.58±0.496 OD, 2.47±0.60 OD)  when compared to control subjects (1.13±0.249 OD, 2.1±0.24 OD), respectively with P=0.001 for both.  Anti-vinculin level was significantly higher in the IBS-D subtype than the other subtypes (P=0.001) while, Anti-CdtB was significantly elevated in IBS-C, IBS-D subgroups compared to control subjects (P=0.001). Conclusion: Findings of the present study support the hypothesis that IBS results from post-infectious disorders initiated by bacterial enteritis. A hypothesis could be applied to all IBS subgroups. On the other hand. These biomarkers might reflect the post-infectious state's severity.

scholarly journals Cell transfection of purified cytolethal distending toxin B subunits allows comparing their nuclease activity while plasmid degradation assay does not

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0214313 ◽  
Author(s):  
Benoît J. Pons ◽  
Elisabeth Bezine ◽  
Mélissa Hanique ◽  
Valérie Guillet ◽  
Lionel Mourey ◽  
...  
Keyword(s):  
Nuclease Activity ◽  
Cell Transfection ◽  
Cytolethal Distending Toxin ◽  
Toxin B ◽  
B Subunits

scholarly journals Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation

2020 ◽  
Vol 88 (10) ◽  
Author(s):  
Ming-xian Chen ◽  
Yu Chen ◽  
Rui Fu ◽  
Guo-qun Mao ◽  
Sai-yue Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Proinflammatory Cytokines ◽  
Cell Types ◽  
Nuclear Factor Κb ◽  
Small Gtpase ◽  
Cytolethal Distending Toxin ◽  
Colonic Epithelial Cells ◽  
Toxin B ◽  
Proinflammatory Responses ◽  
Underlying Mechanisms

ABSTRACT The cytolethal distending toxin B subunit (CdtB) induces significant cytotoxicity and inflammation in many cell types that are involved in the pathogenesis of postinfectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. This study tested the potential role of Rab small GTPase 5a (Rab5a) in the process. We tested mRNA and protein expression of proinflammatory cytokines (interleukin-1β [IL-1β] and IL-6) in THP-1 macrophages by quantitative PCR (qPCR) and enzyme-linked immunosorbent assays (ELISAs), respectively. In the primary colonic epithelial cells, Cdt treatment induced a CdtB-Rab5a-cellugyrin association. Rab5a silencing, by target small hairpin RNAs (shRNAs), largely inhibited CdtB-induced cytotoxicity and apoptosis in colon epithelial cells. CRISPR/Cas9-mediated Rab5a knockout also attenuated CdtB-induced colon epithelial cell death. Conversely, forced overexpression of Rab5a intensified CdtB-induced cytotoxicity. In THP-1 human macrophages, Rab5a shRNA or knockout significantly inhibited CdtB-induced mRNA expression and production of proinflammatory cytokines (IL-1β and IL-6). Rab5a depletion inhibited activation of nuclear factor-κB (NF-κB) and Jun N-terminal protein kinase (JNK) signaling in CdtB-treated THP-1 macrophages. Rab5a appears essential for CdtB-induced cytotoxicity in colonic epithelial cells and proinflammatory responses in THP-1 macrophages.

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