Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.
Ontology highlight
ABSTRACT:
SUBMITTER: Nambu R
PROVIDER: S-EPMC11307533 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.
Nambu R R Mulder D J DJ Nakazawa A A Ishige T T Iwama I I Muise A M AM
Gastro hep advances 20220525 5
Similar Datasets
Project description:Background & aimsAdvances in genomic technologies have led to increasing reports of monogenic inflammatory bowel disease (IBD). Here, we systematically review the literature to determine the clinical features, genetic profile, and previously used treatment strategies in monogenic IBD.MethodsA systematic review of MEDLINE articles published between January 2000 and December 2020 was conducted. A total of 750 individual monogenic IBD cases were identified from 303 eligible articles.ResultsThe most frequently reported monogenic IBD genes were IL10RA/B, XIAP, CYBB, LRBA, and TTC7A. In total, 63.4% of patients developed IBD before 6 years of age, 17.4% developed IBD between ages 10 and 17.9 years, and 10.9% developed IBD after age 18. There was a substantial difference between these age groups and the underlying monogenic disorders. Only 31.7% had any history of extraintestinal comorbidity (EIC) before IBD onset, but 76.0% developed at least 1 EIC during their clinical course. The most common EICs were atypical infection (44.7%), dermatologic abnormality (38.4%), and autoimmunity (21.9%). Bowel surgery, biologic therapy, and hematopoietic stem cell transplantation were performed in 27.1%, 32.9%, and 23.1% of patients, respectively.ConclusionsMonogenic IBD cases, although rare, have varied extraintestinal comorbidities and limited treatment options including surgery and transplant. Early identification and improved understanding of the characteristics of the genes and underlying disease processes in monogenic IBD is important for effective management.
| S-EPMC8448782 | biostudies-literature
Project description:Background & aimsMonogenic forms of inflammatory bowel disease (IBD) illustrate the essential roles of individual genes in pathways and networks safeguarding immune tolerance and gut homeostasis.MethodsTo build a taxonomy model, we assessed 165 disorders. Genes were prioritized based on penetrance of IBD and disease phenotypes were integrated with multi-omics datasets. Monogenic IBD genes were classified by (1) overlapping syndromic features, (2) response to hematopoietic stem cell transplantation, (3) bulk RNA-sequencing of 32 tissues, (4) single-cell RNA-sequencing of >50 cell subsets from the intestine of healthy individuals and patients with IBD (pediatric and adult), and (5) proteomes of 43 immune subsets. The model was validated by addition of newly identified monogenic IBD defects. As a proof-of-concept, we explore the intersection between immunometabolism and antimicrobial activity for a group of disorders (G6PC3/SLC37A4).ResultsOur quantitative integrated taxonomy defines the cellular landscape of monogenic IBD gene expression across 102 genes with high and moderate penetrance (81 in the model set and 21 genes in the validation set). We illustrate distinct cellular networks, highlight expression profiles across understudied cell types (e.g., CD8+ T cells, neutrophils, epithelial subsets, and endothelial cells) and define genotype-phenotype associations (perianal disease and defective antimicrobial activity). We illustrate processes and pathways shared across cellular compartments and phenotypic groups and highlight cellular immunometabolism with mammalian target of rapamycin activation as one of the converging pathways. There is an overlap of genes and enriched cell-specific expression between monogenic and polygenic IBD.ConclusionOur taxonomy integrates genetic, clinical and multi-omic data; providing a basis for genomic diagnostics and testable hypotheses for disease functions and treatment responses.
| S-EPMC7616885 | biostudies-literature
Project description:Crohn's disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.
| S-EPMC4130834 | biostudies-literature
Project description:Thalidomide is an immunomodulatory drug used in the experimental treatment of refractory Crohn disease and ulcerative colitis. We aimed to review the existing evidence on the efficacy and safety of thalidomide in the treatment of inflammatory bowel diseases.CENTRAL, MEDLINE, LILACS, POPLINE, CINHAL, and Web of Science were searched in March 2016. Manual search included conference and reference lists. All types of studies, except single case reports, were included. Outcomes evaluated were: induction of remission; maintenance of remission; steroid reduction; effect on penetrating Crohn disease; endoscopic remission; adverse events.The research strategies retrieved 722 papers. Two randomized controlled trials and 29 uncontrolled studies for a total of 489 patients matched the inclusion criteria. Thalidomide induced a clinical response in 296/427 (69.3%) patients. Clinical remission was achieved in 220/427 (51.5%) cases. Maintenance of remission was reported in 128/160 (80.0%) patients at 6 months and in 96/133 (72.2%) at 12 months. Reduction in steroid dosage was reported in 109/152 (71.7%) patients. Fistulas improved in 49/81 (60.5%) cases and closed in 28/81 (34.6%). Endoscopic improvement was observed in 46/66 (69.7%) and complete mucosal healing in 35/66 (53.0%) patients. Cumulative incidence of total adverse events and of those leading to drug suspension was 75.6 and 19.7/1000 patient-months, respectively. Neurological disturbances accounted for 341/530 (64.3%) adverse events and were the most frequent cause of drug withdrawal.Existing evidence suggests that thalidomide may be a valid treatment option for patients with inflammatory bowel diseases refractory to other first- and second-line treatments.
| S-EPMC5265832 | biostudies-literature
Project description:Inflammatory bowel disease (IBD) is a group of chronic multifactorial disorders. According to a recent study, the number of IBD association loci is increased to 201, of which 37 and 27 loci contribute specifically to the development of Crohn's disease and ulcerative colitis respectively. Some IBD associated genes are involved in innate immunity, in the autophagy and in the inflammatory response such as NOD2, ATG16L1 and IL23R, while other are implicated in immune mediated disease (STAT3) and in susceptibility to mycobacterium infection (IL12B). In case of early onset of IBD (VEO-IBD) within the 6(th) year of age, the disease may be caused by mutations in genes responsible for severe monogenic disorders such as the primary immunodeficiency diseases. In this review we discuss how these monogenic disorders through different immune mechanisms can similarly be responsible of VEO-IBD phenotype. Moreover we would highlight how the identification of pathogenic genes by Next Generation Sequencing technologies can allow to obtain a rapid diagnosis and to apply specific therapies.
| S-EPMC4649114 | biostudies-literature
Project description:Background and aimsUltrasound elastography [USE] is an innovative, non-invasive, promptly available, ancillary technique that has been proposed in the evaluation of intestinal fibrosis as a monitorable biomarker, in terms of stiffness. The non-invasive estimate of fibrosis by USE appears appealing for dedicated physicians, in order to optimise the treatments for inflammatory bowel disease [IBD] patients [surgical vs non-surgical]. We aimed to systematically review literature evidence on ultrasound elastography in IBD patients.MethodsFor this qualitative systematic review, we searched PubMed, EMBASE, and Scopus to identify all studies, published until October 2021, investigating the application of USE in IBD patients compared with histopathological assessment.ResultsOverall, 12 papers published between 2011 and 2019 were included. A total of 275 IBD patients were included: 272 Crohn's disease [CD] [98.9%] and three ulcerative colitis [UC] [1.1%]. Seven [58.3%] and four [41.6%] studies investigated strain elastography [SE] and shear wave elastography [SWE], respectively; in one study [0.1%] both techniques were addressed. The histological evaluation was largely conducted on surgical specimens and in two studies endoscopic biopsies were also included. The histological assessment was semi-quantitative in all the included studies, except for two where the fibrosis was evaluated only qualitatively. In 10/12 publications USE could accurately distinguish inflammation from fibrosis in the examined bowel tracts.ConclusionsFrom the preliminary available data, an overall moderate-to-good accuracy of USE in detecting histological fibrosis [10/12 studies] was found. Point-shear wave elastography has been shown to perform superiorly. Further studies are needed to confirm these evidences.
| S-EPMC9624288 | biostudies-literature
Project description:The aim was to systematically review the evidence on the clinical usefulness of thiopurine metabolite and white blood count (WBC) monitoring in the assessment of clinical outcomes in children with inflammatory bowel disease (IBD).Medline, Embase, Cochrane Central Register of controlled trials and http://www.clinicaltrials.gov were screened in adherence to the PRISMA statement by two independent reviewers for identification of eligible studies. Eligible studies were randomized controlled trials (RCTs), cohort studies and large case series of children with inflammatory bowel disease (IBD) (<18?years) who underwent monitoring of thiopurine metabolites and/or WBC.Fifteen papers were identified (n?=?1026). None of the eligible studies were RCTs. High 6-thioguanine nucleotide (6TGN) concentrations were not consistently associated with leucopenia. Leucopenia was not associated with achievement of clinical remission. A positive but not consistent correlation between 6TGN and clinical remission was reported. Haematological toxicity could not be reliably assessed with 6TGN measurements only. A number of studies supported the use of high 6-methylmercaptopurine ribonucleotides (6MMPR) as an indicator of hepatotoxicity. Low thiopurine metabolite concentration may be indicative of non-compliance.Thiopurine metabolite testing does not safely predict clinical outcome, but may facilitate toxicity surveillance and treatment optimization in poor responders. Current evidence favours the combination of thiopurine metabolite/WBC monitoring and clinic follow-up for prompt identification of haematologic/hepatic toxicity safe dose adjustment, and treatment modification in cases of suboptimal clinical outcome or non-compliance. Well designed RCTs for the identification of robust surrogate markers of thiopurine efficacy and toxicity are required.
| S-EPMC4243898 | biostudies-other
Project description:Background: Given the role of alexithymia-as the inability to identify, differentiate, and express emotions-in chronic and immune-mediated illness, this systematic review analyzed the prevalence of alexithymia in patients with inflammatory bowel diseases (IBDs), mainly represented by Crohn's disease (CD) and ulcerative colitis (UC). Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout this systematic review of the literature published between 2015 and 2020 in indexed sources from PubMed, PsycINFO, Scopus, and Web of Science databases. Search terms for eligible studies were: "Inflammatory bowel disease" AND "Alexithymia" [Titles, Abstract, Keywords]. Inclusion criteria were: articles written and published in English from 2015 and up to April 2020, reporting relevant and empirical data on alexithymia and IBD. Results: The initial search identified 34 indexed scientific publications. After screening, we found that five publications met the established scientific inclusion criteria. Overall, the mean value of alexithymia ranged from 39 to 53.2 [Toronto Alexithymia Scale (TAS-20) score], thus mostly falling in non-clinical range for alexithymia (?51). Comparisons of alexithymia between patients with UC and CD highlighted that patients with CD showed externally oriented thinking and difficulties identifying feelings to a greater extent. Regarding comparisons with other samples or pathologies, patients with IBD were more alexithymic than healthy controls and less alexithymic than patients with major depressive disorder, but no difference was found when compared with patients with irritable bowel syndrome (IBS). Then, regarding correlations with other variables, alexithymia was positively associated with anxiety and depression, as well as with psychopathological symptoms and somatic complaints. Conclusion: This systematic review suggests that patients with IBD cannot be generally considered alexithymic at a clinically relevant extent. However, their greater alexithymic levels and its associations with psychological variables and somatic distress may suggest a reactivity hypothesis, in which living with IBD may progressively lead to impaired emotion recognition over time. Specifically, the relationship between IBD and IBS should be further explored, paying deeper attention to the clinical psychological functioning of CD, as IBD requires more emotional challenges to patients.
| S-EPMC7466427 | biostudies-literature
Project description:BackgroundInflammatory bowel disease (IBD) is a chronic inflammatory immune-mediated disorder of the gut with frequent extra-intestinal complications. Pancreatic involvement in IBD is not uncommon and comprises a heterogeneous group of conditions, including acute pancreatitis (AP), chronic pancreatitis (CP), autoimmune pancreatitis (AIP) and pancreatic exocrine insufficiency (PEI); however, data on such an association remain sparse and heterogeneous.MethodPubMed/MEDLINE and EMBASE databases were searched for studies investigating pancreatic involvement in patients with IBD.ResultsFour thousand one hundred and twenty-one records were identified and 547 screened; finally, 124 studies were included in the review. AP is the most frequent pancreatic manifestation in IBD; the majority of AP cases in IBD are due to gallstones and drugs but cases of idiopathic AP are increasingly reported. AIP is a rare disease, but a strong association with IBD has been demonstrated, especially for type 2 and ulcerative colitis. The pathogenetic link between IBD and AIP remains unclear, but an immune-mediated pathway seems plausible. An association between CP and PEI with IBD has also been suggested, but data are to date scarce and conflicting.ConclusionThis is the first systematic review of the association between IBD and pancreatic diseases. Gallstones and drugs should be considered the most probable causes of AP in IBD, with type 2 AIP also being possible.
| S-EPMC9322673 | biostudies-literature
Project description:Background and aimsOver 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES].MethodsPatients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns.ResultsThis analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn's disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes.ConclusionsMonogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD.
| S-EPMC9455789 | biostudies-literature