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Crohn Disease: HELP
Articles by Abdul A. Elkadri
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Abdul Elkadri wrote the following 7 articles about Crohn Disease.
 
+ Citations + Abstracts
1 Review The diagnostic approach to monogenic very early onset inflammatory bowel disease. 2014

Uhlig, Holm H / Schwerd, Tobias / Koletzko, Sibylle / Shah, Neil / Kammermeier, Jochen / Elkadri, Abdul / Ouahed, Jodie / Wilson, David C / Travis, Simon P / Turner, Dan / Klein, Christoph / Snapper, Scott B / Muise, Aleixo M / Anonymous2530801. ·Translational Gastroenterology Unit, University of Oxford, Oxford, England; Department of Pediatrics, University of Oxford, Oxford, England. Electronic address: holm.uhlig@ndm.ox.ac.uk. · Translational Gastroenterology Unit, University of Oxford, Oxford, England. · Dr von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany. · Great Ormond Street Hospital London, London, England; Catholic University, Leuven, Belgium. · Great Ormond Street Hospital London, London, England. · SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. · Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts; Division of Gastroenterology and Hepatology, Brigham & Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts. · Child Life and Health, University of Edinburgh, Edinburgh, Scotland; Department of Pediatric Gastroenterology, Hepatology, and Nutrition, Royal Hospital for Sick Children, Edinburgh, Scotland. · Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel. ·Gastroenterology · Pubmed #25058236.

ABSTRACT: Patients with a diverse spectrum of rare genetic disorders can present with inflammatory bowel disease (monogenic IBD). Patients with these disorders often develop symptoms during infancy or early childhood, along with endoscopic or histological features of Crohn's disease, ulcerative colitis, or IBD unclassified. Defects in interleukin-10 signaling have a Mendelian inheritance pattern with complete penetrance of intestinal inflammation. Several genetic defects that disturb intestinal epithelial barrier function or affect innate and adaptive immune function have incomplete penetrance of the IBD-like phenotype. Several of these monogenic conditions do not respond to conventional therapy and are associated with high morbidity and mortality. Due to the broad spectrum of these extremely rare diseases, a correct diagnosis is frequently a challenge and often delayed. In many cases, these diseases cannot be categorized based on standard histological and immunologic features of IBD. Genetic analysis is required to identify the cause of the disorder and offer the patient appropriate treatment options, which include medical therapy, surgery, or allogeneic hematopoietic stem cell transplantation. In addition, diagnosis based on genetic analysis can lead to genetic counseling for family members of patients. We describe key intestinal, extraintestinal, and laboratory features of 50 genetic variants associated with IBD-like intestinal inflammation. In addition, we provide approaches for identifying patients likely to have these disorders. We also discuss classic approaches to identify these variants in patients, starting with phenotypic and functional assessments that lead to analysis of candidate genes. As a complementary approach, we discuss parallel genetic screening using next-generation sequencing followed by functional confirmation of genetic defects.

2 Article Impaired antibacterial autophagy links granulomatous intestinal inflammation in Niemann-Pick disease type C1 and XIAP deficiency with NOD2 variants in Crohn's disease. 2017

Schwerd, Tobias / Pandey, Sumeet / Yang, Huei-Ting / Bagola, Katrin / Jameson, Elisabeth / Jung, Jonathan / Lachmann, Robin H / Shah, Neil / Patel, Smita Y / Booth, Claire / Runz, Heiko / Düker, Gesche / Bettels, Ruth / Rohrbach, Marianne / Kugathasan, Subra / Chapel, Helen / Keshav, Satish / Elkadri, Abdul / Platt, Nick / Muise, Alexio M / Koletzko, Sibylle / Xavier, Ramnik J / Marquardt, Thorsten / Powrie, Fiona / Wraith, James E / Gyrd-Hansen, Mads / Platt, Frances M / Uhlig, Holm H. ·Translational Gastroenterology Unit, University of Oxford, Oxford, UK. · Nuffield Department of Clinical Medicine, Ludwig Institute for Cancer Research, University of Oxford, Oxford, UK. · Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, Saint Mary's Hospital, Manchester, UK. · National Hospital for Neurology and Neurosurgery, London, UK. · Great Ormond Street Hospital, London, UK. · NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. · Department of Clinical Immunology, Great Ormond Street Hospital, London, UK. · University of Heidelberg, Heidelberg, Germany. · University Children's Hospital Bonn, Bonn, Germany. · Children's Hospital Münster, Münster, Germany. · Children's Research Centre Zurich, University Children's Hospital, Zurich, Switzerland. · Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, Georgia, USA. · SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. · Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. · Department of Pharmacology, University of Oxford, Oxford, UK. · Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany. · Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. · Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK. · Department of Pediatrics, University of Oxford, Oxford, UK. ·Gut · Pubmed #26953272.

ABSTRACT: OBJECTIVE: Patients with Niemann-Pick disease type C1 (NPC1), a lysosomal lipid storage disorder that causes neurodegeneration and liver damage, can present with IBD, but neither the significance nor the functional mechanism of this association is clear. We studied bacterial handling and antibacterial autophagy in patients with NPC1. DESIGN: We characterised intestinal inflammation in 14 patients with NPC1 who developed IBD. We investigated bacterial handling and cytokine production of NPC1 monocytes or macrophages in vitro and compared NPC1-associated functional defects to those caused by IBD-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) variants or mutations in X-linked inhibitor of apoptosis (XIAP). RESULTS: Patients with the lysosomal lipid storage disorder NPC1 have increased susceptibility to early-onset fistulising colitis with granuloma formation, reminiscent of Crohn's disease (CD). Mutations in NPC1 cause impaired autophagy due to defective autophagosome function that abolishes NOD2-mediated bacterial handling in vitro similar to variants in NOD2 or XIAP deficiency. In contrast to genetic NOD2 and XIAP variants, NPC1 mutations do not impair NOD2-receptor-interacting kinase 2 (RIPK2)-XIAP-dependent cytokine production. Pharmacological activation of autophagy can rescue bacterial clearance in macrophages in vitro by increasing the autophagic flux and bypassing defects in NPC1. CONCLUSIONS: NPC1 confers increased risk of early-onset severe CD. Our data support the concept that genetic defects at different checkpoints of selective autophagy cause a shared outcome of CD-like immunopathology linking monogenic and polygenic forms of IBD. Muramyl dipeptide-driven cytokine responses and antibacterial autophagy induction are parallel and independent signalling cascades downstream of the NOD2-RIPK2-XIAP complex.

3 Article The operative management of children with complex perianal Crohn's disease. 2016

Seemann, Natashia M / King, Sebastian K / Elkadri, Abdul / Walters, Thomas / Fish, Joel / Langer, Jacob C. ·Division of General and Thoracic Surgery, Hospital for Sick Children, Department of Surgery, University of Toronto. · Division of Gastroenterology, Hospital for Sick Children, Department of Pediatrics, University of Toronto. · Division of Plastic and Reconstructive Surgery, Hospital for Sick Children, Department of Surgery, University of Toronto. · Division of General and Thoracic Surgery, Hospital for Sick Children, Department of Surgery, University of Toronto. Electronic address: jacob.langer@sickkids.ca. ·J Pediatr Surg · Pubmed #27692346.

ABSTRACT: BACKGROUND/PURPOSE: Perianal Crohn's disease (PCD) can affect both quality of life and psychological wellbeing. A subset of pediatric patients with complex PCD require surgical intervention, although appropriate timing and treatment regimens remain unclear. This study aimed to describe a large pediatric cohort in a tertiary center to determine the range of surgical management in children with complex PCD. METHODS: A retrospective review of children requiring operative intervention for PCD over 13 years (2002-2014) was performed. PCD was divided into simple and complex based on the type of surgical procedure, and the two groups were compared. RESULTS: The 57 children were divided into two groups: the simple group (N=43) underwent abscess drainage ± seton insertion alone, and the complex group (N=14) underwent loop ileostomy ± more extensive surgery. In the complex group, females were more predominant (57% of complex vs 30% of simple), and the average age at diagnosis was lower. Anti-TNF therapy was utilized in 79.1% of simple and 100% of complex PCD. All 14 complex patients underwent a defunctioning ileostomy, with 7 requiring further operations (subtotal colectomy=4, proctocolectomy ± anal sparing=5, plastic surgery reconstruction with perineal flap/graft=4). CONCLUSION: Complex PCD represents a small but challenging subset of patients in which major surgical intervention may be necessary to alleviate the symptoms of this debilitating condition. LEVEL OF EVIDENCE: retrospective case study with no control group - level IV.

4 Article Mucosa-Associated Ileal Microbiota in New-Onset Pediatric Crohn's Disease. 2016

Assa, Amit / Butcher, James / Li, Jennifer / Elkadri, Abdul / Sherman, Philip M / Muise, Aleixo M / Stintzi, Alain / Mack, David. ·*Cell Biology Program, Research Institute; †Department of Paediatrics, Hospital for Sick Children; ‡University of Toronto, Toronto; §Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa; ‖CHEO Research Institute; and ¶Department of Paediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada. ·Inflamm Bowel Dis · Pubmed #27271491.

ABSTRACT: BACKGROUND: The composition of the intestinal microbiome seems relevant to the pathogenesis of Crohn's disease (CD), with differences in both diversity and composition of the gut microbiota in patients with CD compared with healthy individuals. However, there are still conflicting reports on the importance of various bacterial taxa in the pathogenesis of CD. The aim of this study was to characterize the composition of mucosa-associated intestinal microbiota in newly diagnosed pediatric patients with CD. METHODS: Mucosa-associated bacteria were identified from ileal biopsy specimens obtained at colonoscopy of 10 patients with either ileal or ileocolonic new-onset CD and 15 controls without mucosal inflammation. Microbial composition was performed by profiling the 16S rDNA V6 region using Illumina sequencing. Samples were analyzed for differences in alpha/beta diversity and also for differentially abundant taxa. RESULTS: Alpha diversity did not differ between the controls and CD cases or between CD subjects with localized ileal disease compared with those with more extensive disease. Controls also did not clearly separate from patients with CD by principal coordinate analyses; however, 117 operational taxonomic units were found to be differentially abundant between the two groups. In particular, numerous operational taxonomic units associated with Faecalibacterium prausnitzii species were increased in children with CD. CONCLUSIONS: These findings contribute to emerging evidence regarding dysbiosis in pediatric CD, and provide additional evidence challenging the protective role of F. prausnitzii in CD.

5 Article Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early-Onset Inflammatory Bowel Disease. 2016

Li, Qi / Lee, Cheng Hiang / Peters, Lauren A / Mastropaolo, Lucas A / Thoeni, Cornelia / Elkadri, Abdul / Schwerd, Tobias / Zhu, Jun / Zhang, Bin / Zhao, Yongzhong / Hao, Ke / Dinarzo, Antonio / Hoffman, Gabriel / Kidd, Brian A / Murchie, Ryan / Al Adham, Ziad / Guo, Conghui / Kotlarz, Daniel / Cutz, Ernest / Walters, Thomas D / Shouval, Dror S / Curran, Mark / Dobrin, Radu / Brodmerkel, Carrie / Snapper, Scott B / Klein, Christoph / Brumell, John H / Hu, Mingjing / Nanan, Ralph / Snanter-Nanan, Brigitte / Wong, Melanie / Le Deist, Francoise / Haddad, Elie / Roifman, Chaim M / Deslandres, Colette / Griffiths, Anne M / Gaskin, Kevin J / Uhlig, Holm H / Schadt, Eric E / Muise, Aleixo M. ·SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada. · Gastroenterology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; The James Fairfax Institute of Paediatric Nutrition, University of Sydney, New South Wales, Australia. · Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York. · Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada. · SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. · Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, Experimental Medicine Division, University of Oxford and Department of Pediatrics, John Radcliffe Hospital, Oxford, UK. · Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai and the Icahn Institute for Genomics and Multiscale Biology, New York, New York. · Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany. · Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada. · Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. · Janssen R&D, LLC, Spring House, Pennsylvania. · Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology and Hepatology, Brigham & Women's Hospital, Department of Medicine, Boston, Massachusetts. · SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. · Immunology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia. · Department of Microbiology and Immunology, CHU Sainte Justine and Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada. · Department of Pediatrics, CHU Sainte-Justine, Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada. · Division of Immunology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. · Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada. · SickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Toronto, Hospital for Sick Children, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada. Electronic address: aleixo.muise@utoronto.ca. ·Gastroenterology · Pubmed #26836588.

ABSTRACT: BACKGROUND & AIMS: Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents. METHODS: We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very-early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment-resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture. RESULTS: We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon-beta signaling and nuclear factor-κB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores. CONCLUSIONS: In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD.

6 Article The role of surgery for children with perianal Crohn's disease. 2015

Seemann, Natashia M / Elkadri, Abdul / Walters, Thomas D / Langer, Jacob C. ·Department of Surgery, University of Toronto, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada. · Institute of Medical Science, University of Toronto, Toronto, ON, Canada; Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada. · Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada. · Department of Surgery, University of Toronto, Toronto, ON, Canada; Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: jacob.langer@sickkids.ca. ·J Pediatr Surg · Pubmed #25598111.

ABSTRACT: PURPOSE: Children with perianal Crohn's disease (PCD) are a unique and diverse patient population. The purpose of this study was to describe the spectrum of disease and role of surgery. METHODS: A retrospective chart review of all children having at least one surgical intervention for PCD over 10 years was performed. RESULTS: Fifty-seven patients (63% male) aged 0.5-17 (median 13) years were identified. Perianal disease consisted of skin tags (49%), superficial fistulae (49%), deep fistulae (37%), superficial abscesses (68%), deep abscesses (9%), skin breakdown (19%), and anal strictures (7%). 84% received anti-TNF therapy, with 27% treated with a second anti-TNF medication. Minor surgical procedures, commonly done during anti-TNF therapy, included abscess drainage (67%) and seton placement (33%). Major surgical procedures, done almost exclusively after anti-TNF failure, included defunctioning ileostomy (23%) and subtotal colectomy (9%). Follow-up ranged from 7 to 160 (median 54) months. CONCLUSIONS: Pediatric PCD has a wide range of disease severity. Minor surgery provides adequate drainage before and during anti-TNF therapy, while major surgery plays a role in medically refractory disease. Appropriate surgical intervention remains an important part of the treatment paradigm.

7 Article Serum antibodies associated with complex inflammatory bowel disease. 2013

Elkadri, Abdul A / Stempak, Joanne M / Walters, Thomas D / Lal, Simon / Griffiths, Anne M / Steinhart, A Hillary / Silverberg, Mark S. ·The Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. ·Inflamm Bowel Dis · Pubmed #23702714.

ABSTRACT: BACKGROUND: Antibodies to microbial antigens have been associated with specific diagnoses and phenotypes of inflammatory bowel disease. We evaluated the prevalence of pANCA, IgA and IgG anti-Saccharomyces cerevisiae antibodies, anti-OmpC, and anti-flagellin in a large well-defined population of patients with Crohn's disease (CD) and ulcerative colitis (UC) and analyzed for various clinical outcomes. METHODS: Samples were collected from 391 patients with CD, 207 patients with UC, and 62 healthy controls. Patients were phenotyped using the Montreal classification. Blinded serological analyses were performed for pANCA, IgA and IgG anti-Saccharomyces cerevisiae antibodies, anti-OmpC, and anti-flagellin. RESULTS: In CD, increasing quantitative levels for antibodies were associated with a younger age of diagnosis, longer disease duration, increased surgeries, ileocolonic and perianal disease, and internal perforating behavior. In UC, they were associated with colectomy. An increasing number of seropositive antibodies in CD was associated with a younger age at diagnosis, increased disease duration, ileocolonic and perianal disease, internal penetrating and stricturing behavior, and increased surgeries. Multivariate analysis confirmed the association of antimicrobial antibodies with features of complicated CD and UC. CONCLUSIONS: Increased serological markers are associated with a more aggressive CD phenotype and an increased need for colectomy in UC. This raises the possibility for use of these markers in patients at risk of complex disease.