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Evidence for the involvement of infectious agents in the pathogenesis of Crohn's disease

World Journal of Gastroenterology 2008年第6期14卷 845-852页

作者： gert de hertogh Jeroen Aerssens Karen P Geboes Karel Geboes Karel Geboes Department of Pathology University Hospitals KULeuven Minderbroedersstraat 12 Leuven 3000 Belgium Tibotec bvba Generaal De Wittelaan L 11B 3 Mechelen 2800 Belgium department of Gastroenterology University Hospitals KULeuven Herestraat 49 Leuven 3000 Belgium

Many advances have been made in the understanding of Crohn’s disease (CD) pathogenesis during the last decade. CD is currently seen as a predominantly T-lym-phocyte-driven disease characterized by the presence of a complex cocktail of interacting cytokines, chemokines and other mediators produced by a variety of cell types. Prevailing theories of CD pathogenesis suggest that patients’ T-lymphocytes are inappropriately activated in the setting of an immune imbalance, which is itself caused by an unfortunate confluence of genetic and en- vironmental factors. The T-cell response then leads to the chronic inflammation characteristic for the disease. Various environmental factors may play a role in the development of CD, but microbes are most consistently implied. This theory is based on epidemiological, clinico- pathological, genetic and experimental evidence. despite the abundance of arguments for the implication of bac-teria in the aetiopathogenesis of CD, the precise role of bacteria in this disease still remains elusive. Three not necessarily mutually exclusive theories have been pro- posed: (1) an unidentified persistent pathogen; (2) an abnormally permeable mucosal barrier leading to exces-sive bacterial translocation; and (3) a breakdown in the balance between putative "protective" versus "harmful" intestinal bacteria ("dysbiosis"). At present, one cannot exclude with certainty any of these three proposed hy-potheses; they may all apply to CD to a certain extent.

关键词： Crohn's disease Etiology Microbiology

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On the origin of cardiac mucosa: A histological and immunohistoc-hemical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach

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World Journal of Gastroenterology 2005年第29期11卷 4490-4496页

作者： gert de hertogh Peter Van Eyken Nadine Ectors Karel Geboes department of Morphology and Molecular Pathology University Hospitals KU Leuven Leuven Belgium

AIM： To examine the fetal and neonatal esophagogastric junction region （EGJ） histologically for the presence of an equivalent to adult cardiac mucosa （CM）; to study the expression patterns of all cytokeratins （CK） relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. METHODS： Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin （H＆E） to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. RESULTS： The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age （GA）. The proximal part of this segment consisted of mucusproducing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the coordinate CK7＋/20＋ and the CK7-/20- immunophenotypes between different locations. The prevalence of the CK7＋/ 20- immunophenotype decreased, and that of the CK7-/ 20＋ immunophenotype increased significantly from the distal esophagus to the distal stomach. CONCLUSION： Fetal columnar-lined lower esophagus （fetal CLE） may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells （ESN） may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression pattems support the conclusion that adult CN has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.

关键词： Cardiac mucosa Origin Fetal autopsy Barrett's CK7/20 pattern

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T(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas are heterogeneous with respect to the V_H gene mutation status

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World Journal of Gastrointestinal Oncology 2011年第2期3卷 24-32页

作者： Xavier Sagaert Vera Vanhentenrijk gert de hertogh Karel Geboes Thomas Tousseyn Brigitte Maes Mathijs Baens Eric Van Cutsem department of Morphology and Molecular Pathology University Hospitals Leuven department of Morphology and Molecular Pathology University Hospitals Leuven department of Laboratory Medicine Jessa Hospital department for Molecular and developmental Genetics Flanders Institute for Biotechnology (VIB) department of Human Genetics Catholic University of Leuven department of Digestive Oncology University Hospitals Leuven

AIM: To investigate how t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas relate to other marginal zone lymphomas with respect to the somatic mutation pattern of the VH genes and the expression of the marker CD27. METHODS: The VH gene of 7 t(11;18)(q21;q21)-positive gastrointestinal MALT lymphomas was amplif iedby PCR using family specif ic VH primers and a consensus JH primer. PCR products were sequenced and mutation analysis of the CDR and the FR regions was performed. All cases were immunostained for CD27. RESULTS: One case showed unmutated VH genes while the others showed mutated VH genes with mutation frequencies ranging from 1.3 to 14.7% and with evidence of antigen selection in 2 cases. These data suggest that the translocation t(11;18)(q21;q21) can target either B-cells at different stages of differentiation or naive B-cells that retain the capacity to differentiate upon antigen stimulation. All cases but one displayed weak to strong CD27 expression which did not correlate with the VH gene mutation status. CONCLUSION: t(11;18)(q21;q21)-positive gastro- intestinal MALT lymphomas are heterogeneous with respect to the VH mutation status and CD27 is not a marker of somatically mutated B-cells.

关键词： Gastrointestinal MALT lymphoma t(11 18) (q21 q21) VH mutation Marginal zone CD27

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Potential importance of early treatment of SARS-CoV-2 infection in intestinal transplant patient: A case report

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World Journal of Transplantation 2022年第4期12卷 72-78页

作者： Mathias Clarysse Laurens J Ceulemans Lucas Wauters Nicholas Gilbo Viktor Capiau gert de hertogh Wim Laleman Chris Verslype Diethard Monbaliu Jacques Pirenne Tim Vanuytsel department of Abdominal Transplant Surgery&Transplant Coordination University Hospitals LeuvenLeuven 3000Vlaams-BrabantBelgium Leuven Intestinal Failure and Transplantation Center(LIFT) University Hospitals LeuvenLeuven 3000Vlaams-BrabantBelgium Laboratory of Abdominal Transplant Surgery Department of MicrobiologyImmunology and TransplantationKU LeuvenLeuven 3000Vlaams-BrabantBelgium department of Thoracic Surgery University Hospitals LeuvenLeuven 3000Vlaams-BrabantBelgium Laboratory of Respiratory Diseases and Thoracic Surgery(BREATHE) Department of Chronic Diseases and Metabolism(CHROMETA)KU LeuvenLeuven 3000Vlaams-BrabantBelgium department of Gastroenterology and Hepatology University Hospitals LeuvenLeuven 3000Vlaams-BrabantBelgium Translational Research Center for Gastrointestinal Disorders(TARGID) Department Chronic Diseases and Metabolism(CHROMETA)KU LeuvenLeuven 3000Vlaams-BrabantBelgium department of Pathology University Hospitals LeuvenLeuven 3000Vlaams-BrabantBelgium Laboratory of Translational Cell&Tissue Research KU LeuvenLeuven 3000Vlaams-BrabantBelgium Laboratory of Clinical Digestive Oncology Department of Digestive OncologyKU LeuvenLeuven 3000Vlaams-BrabantBelgium

BACKGROUND Predispositions for severe coronavirus disease 2019(COVID-19)are age,immunosuppression,and *** levels of maintenance immunosuppression render intestinal transplant(ITx)patients vulnerable for severe ***-19 also provokes several gastroenterological pathologies which have not been discussed in ITx,so *** SUMMARY During the second European COVID-19 wave in November 2020,an ITx recipient was admitted to the hospital because of electrolyte disturbances due to *** consisted of tacrolimus,azathioprine,and low-dose *** hospitalization,she tested positive on screening COVID-19 nasopharyngeal polymerase chain reaction swab,while her initial test was *** was initially asymptomatic and had normal inflammatory *** levels were slightly raised,as Azathioprine was temporarily *** to elevated Ddimers at that time,prophylactic low-molecular weight heparin was *** days after the positive test,dyspnea,anosmia,and C-reactive protein increase(25 mg/L)were *** was administered during 5 d in *** stomal output was noted in two consecutive days and several days *** exclude infection or rejection,an ileoscopy and biopsy were performed and excluded *** weeks later,she was discharged from the hospital and remains in good health since *** Early eradication of severe acute respiratory syndrome coronavirus 2 in ITx recipients may be warranted to prevent acute rejection provocation by it.

关键词： COVID-19 Intestinal transplantation Outcome SARS-CoV-2 Treatment Case report

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