scholarly journals P047 The ATG16L1 T300A polymorphism in Crohn’s Disease patients leads to abnormal autophagy flux in dendritic cells

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S155-S156
Author(s):  
G Quiniou ◽  
O Dinet ◽  
O Cervantes ◽  
M Verdet ◽  
G Boschetti ◽  
...  

Abstract Background Crohn’s disease is a chronic inflammatory bowel disease, whose pathogenesis is largely determined by an inappropriate immune response towards luminal microbiota in genetically susceptible hosts, affecting in particular genes involved in the autophagy process. The autophagy-related ATG16L1 T300A variant is one of the most frequently associated polymorphisms with susceptibility to Crohn’s disease, but the functional consequences of this polymorphism on the dynamic properties of the autophagy flux remains unknown. Methods Using dynamic monitoring of LC3 lipidation, a key protein marker of autophagy, we have quantitatively analysed the autophagic flux of human primary dendritic cells, which are very potent antigen-presenting cells whose function is critical in Crohn’s disease. Results The detailed analysis of the dynamic properties of the autophagic flux reveal that the maturation process in dendritic cells from healthy subjects is associated with a decrease of the velocity and the intensity on the autophagy flux although the turnover of autophagosome formation was maintained, demonstrating the capacity of resilience of the autophagy flux for a maintenance of functional autophagy during maturation process. Strikingly, the expression of the ATG16L1 T300A variant, but not NOD2 R702W variant, in dendritic cells from patients with Crohn’s disease is associated with a disorder of the autophagic flux dynamics in immature dendritic cells, that was not modulated upon maturation. The lack of adaptation of the autophagy flux in ATG16L1 T300A expressing dendritic cells of Crohn’s disease patients, during their maturation was not associated with altered phenotypic acquisition of maturation markers but highlighted a very specific autophagic flux signature. Conclusion Dendritic cells of Crohn’s patients expressing the autophagy-related ATG16L1 T300A have an altered autophagy flux, that could affect their function and contribute to the pathogenesis of Crohn’s disease.

2017 ◽  
Vol 6 (2) ◽  
Author(s):  
Matilde Zamboni ◽  
Maria Grazia Sibilla ◽  
Roberto Galeotti ◽  
Massimo Pedriali ◽  
Simona Ascanelli

Crohn’s disease (CD) is a chronic inflammatory bowel disease and its pathogenesis is still not well understood. Previous studies suggested the possibility of the involvement of vascular system, but, todate, the mesenteric circulation has poor been investigated, especially in complicated CD cases requiring colectomy. We investigated the mesenteric circulation in a case-control pilot study, including 19 controls and 7 patients affected by complicated cases of CD. Cases and controls underwent selective angiography of both superior and inferior mesenteric district. Transit time was found either significantly shortened in 2/7 cases (29%), or prolonged 5/7 (71%) (P=0.0034 in the superior mesenteric district; P=0.0079 in the inferior mesenteric district), respectively due to the presence of A-V malformations and of a miscellaneous of venous abnormalities, which included thrombosis, hypoplasia and extra-truncular venous malformations. Our study demonstrates the presence of congenital or acquired vascular anomalies in a small sample of CD patients not responder to current treatment and with severe complications. The present pilot study warrants further investigations.


Gut ◽  
2010 ◽  
Vol 59 (Suppl 1) ◽  
pp. A63.1-A63
Author(s):  
A U Murugananthan ◽  
D O Bernardo ◽  
C T Tee ◽  
N Arebi ◽  
S C Knight ◽  
...  

1985 ◽  
Vol 33 (12) ◽  
pp. 604-609
Author(s):  
Roberta Messner ◽  
Sylvia Gardner ◽  
Susan Lewis

Crohn's disease is a chronic, inflammatory bowel disease which may occur in single or multiple areas of the entire GI tract from the mouth to the anus. This multifaceted disorder is manifested by various unpredictable health disturbances, affecting its victims' physical and psychosocial well-being. Individuals with Crohn's disease present a multitude of nursing challenges as they often lack the positive effects of proper nutrition, physical activity, emotional expression, interpersonal relationships, and family life. Nurses are the primary care providers who can comprehensively address the varied and complex health care needs of individuals with Crohn's disease. The core theme is the belief that it is essential for these individuals to maintain a sense of control in the midst of an altered lifestyle. Occupational health nurses can assist employees with Crohn's disease to develop a variety of physical and psychosocial strategies to cope with the unpleasant, even repugnant, aspects of a disease for which there is no known cure. The promotion of optimal health, based on the nursing process, is the objective toward which the unique efforts of nursing are directed.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2947 ◽  
Author(s):  
Lidia Santarpia ◽  
Lucia Alfonsi ◽  
Fabiana Castiglione ◽  
Maria Carmen Pagano ◽  
Iolanda Cioffi ◽  
...  

Background: Crohn’s disease (CD) is a chronic inflammatory bowel disease frequently associated with malabsorption and secondary protein-energy malnutrition (PEM). Methods: Biochemical and clinical data of 63 (34 females, 29 males) patients with PEM due to CD sent to our outpatient unit for nutritional evaluation were retrospectively analyzed. Patients were divided into two groups, according to disease activity. Thirty-eight patients (group A) had the active disease, and 25 patients (group B) suffered from malabsorption resulting from past intestinal resections due to CD. After a physical and hemato-biochemical evaluation at the first visit, all patients received disease-specific personalized dietetic indications. When indicated, oral nutritional supplements, oral/parenteral vitamins, micronutrients, and electrolytes, up to parenteral nutrition, were prescribed. Results: After 1, 3, and 6 months of nutritional therapy, body weight, body mass index (BMI), and serum butyryl-cholinesterase significantly improved in both groups. In 8 out of 13 (61.5%) patients with a cutaneous stoma, intestinal continuity was restored. Conclusions: This study confirms the effectiveness of nutritional rehabilitation and provides information on the time required for nutritional treatment in patients with CD, both during the acute phase and after malabsorption due to intestinal resection.


2003 ◽  
Vol 124 (4) ◽  
pp. A324
Author(s):  
Osamu Hitotsumatsu ◽  
Nagamu Inoue ◽  
Hiromasa Takaishi ◽  
Haruhiko Ogata ◽  
Yasushi Iwao ◽  
...  

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Nathalie Taquet ◽  
Serge Dumont ◽  
Jean-Luc Vonesch ◽  
Didier Hentsch ◽  
Jean-Marie Reimund ◽  
...  

Crohn's disease (CD) is a multifactorial chronic inflammatory bowel disease of unknown cause. The aim of the present study was to explore if mRNA over-expression of SSTR5 and CCR7 found in CD patients could be correlated to respective protein expression. When compared to healthy donors, SSTR5 was over-expressed 417±71 times in CD peripheral blood mononuclear cells (PBMCs). Flow cytometry experiments showed no correlation between mRNA and protein expression for SSTR5 in PBMCs. In an attempt to find a reason of such a high mRNA expression, SSTR5 present on CD PBMCs were tested and found as biologically active as on healthy cells. In biopsies of CD intestinal tissue, SSTR5 was not over-expressed but CCR7, unchanged in PBMCs, was over-expressed by 10±3 times in the lamina propria. Confocal microscopy showed a good correlation of CCR7 mRNA and protein expression in CD intestinal biopsies. Our data emphasize flow and image cytometry as impossible to circumvent in complement to molecular biology so to avoid false interpretation on receptor expressions. Once confirmed by further large-scale studies, our preliminary results suggest a role for SSTR5 and CCR7 in CD pathogenesis.


2016 ◽  
Vol 2 (11) ◽  
Author(s):  
Adriana Georgiana Olariu ◽  
Liliana Bordeianou

<p>Crohn’s disease (CD) is a chronic inflammatory bowel disease with a relapsing, remitting course.  Approximately one in four CD patients requires surgery within five years of diagnosis. Unfortunately, surgery is rarely curative and up to 70% of CD patients experience endoscopic recurrence and 40% have clinical disease recurrence within 18 months after surgery.</p><p> </p><p>This review is aimed at providing internists and gastroenterologists a foundation for the management of patients who underwent ileocecal resection for CD. We provide an overview of the current definitions of postoperative recurrence and prognostic factors for postoperative CD recurrence. As recent studies raised concerns about the value of these factors, we examine the evidence behind the current risk stratification algorithm and pharmacologic treatment recommendations. Lastly, we discuss future directions for research.</p>


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