scholarly journals Gene Polymorphisms of NOD2, IL23R, PTPN2 and ATG16L1 in Patients with Crohn’s Disease: On the Way to Personalized Medicine?

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 866
Author(s):  
Peter Hoffmann ◽  
David Lamerz ◽  
Petra Hill ◽  
Marietta Kirchner ◽  
Annika Gauss

Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn’s disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.

2021 ◽  
Vol 64 (9) ◽  
pp. 605-613
Author(s):  
Hyo Yeop Song ◽  
Geom Seog Seo

Background: The treatment of inflammatory bowel diseases has evolved with the development of anti-tumor necrosis factor agents. Despite the long-term effectiveness, many patients experience primary non-response, secondary loss of response, or intolerance. Therefore, the development of new drugs that act on different inflammatory pathways has become necessary. This review focuses on biologic agents and new therapies for the treatment of inflammatory bowel diseases.Current Concepts: Vedolizumab, a gut-selective agent that targets α4β7 integrin is effective in both ulcerative colitis and Crohn’s disease. Ustekinumab is a monoclonal antibody that binds to p40 subunit of interleukin-12/interleukin-23. Ustekinumab is available for the treatment of Crohn’s disease and ulcerative colitis. Tofacitinib is the first Janus kinase inhibitor approved for the treatment of ulcerative colitis. The advantage of tofacitinib is an oral prescription medicine and has rapid action.Discussion and Conclusion: Since vedolizumab, ustekinumab and tofacitinib are effective agents for the treatment of inflammatory bowel diseases, positioning of old and new biologic agents and small molecules should be determined. The safety and efficacy of novel and emerging drugs needs to be evaluated in patients with inflammatory bowel disease.


2021 ◽  
Vol 9 ◽  
pp. 2050313X2110086
Author(s):  
Arieh Gomolin ◽  
Hanieh Zargham ◽  
Ana Maria Sant’Anna ◽  
Audrey Lovett

Children with vulvar swelling often present to multiple physicians and face a prolonged period of ambiguity and extraneous treatments. Here, we report a case of an 8-year-old girl who presented to the dermatology clinic with a 2-month history of vulvar swelling and was ultimately diagnosed with Crohn’s disease. Although extra-intestinal manifestations are common in inflammatory bowel diseases, they rarely present before an existing diagnosis. This report highlights this potential early manifestation and demonstrates how timely diagnosis leads to improved outcomes for patients, their families, and healthcare systems.


2020 ◽  
Vol 57 (3) ◽  
pp. 311-315 ◽  
Author(s):  
Manoel Álvaro de Freitas LINS NETO ◽  
Giulia Maria Ximenes VERDI ◽  
Arthur de Oliveira VERAS ◽  
Matheus de Oliveira VERAS ◽  
Luiz Carlos CAETANO ◽  
...  

ABSTRACT BACKGROUND: Crohn’s disease and ulcerative colitis are the primary inflammatory bowel diseases (IBD), and its pathogenesis is related to genetic and environmental factors. Currently, the diagnosis of IBD results in a multidisciplinary approach with significant disadvantages, such as its invasive nature, time spent, and the fact that 10% of patients remain without diagnostic classification. However, new methodologies of analysis have emerged that allowed the expansion of knowledge about IBD, as the metabolomics, the study of metabolites. The presence and prevalence of such metabolites may prove to be useful as biomarkers in the diagnosis of IBD. OBJECTIVE: Analyze fecal samples for metabolic analysis in the diagnosis of inflammatory bowel diseases (IBD), providing differentiation between Crohn’s disease and ulcerative colitis. METHODS: This is an observational study with 21 patients diagnosed with IBD (ulcerative colitis 11 and Crohn’s disease 10) and 15 healthy controls, all with the consent and clarification. The fecal extracts of all patients are submitted to a high-resolution Nuclear Magnetic Resonance Hydrogen (1H-NMR) spectroscopy combined with multivariate and univariate pattern recognition techniques. Through the metabolomics of fecal extracts, gives us a characterization of employing a noninvasive approach. RESULTS: We identify some metabolites, such as lactate, succinate, alanine, and tyrosine, in the Crohn’s disease fecal samples, and leucine, alanine, and tyrosine in the ulcerative colitis fecal samples. All the amino acids presented positive covariance for disease correlation. CONCLUSION: The results showed different metabolic profiles between IBD patients and healthy volunteers based on 1H-NMR analysis of fecal extracts. Moreover, the approach discriminated patients with Crohn’s disease and ulcerative colitis. The metabolomics analysis is promising as a novel diagnostic technique for further IBD recognition and surveillance. New studies are necessary to validate these findings.


1988 ◽  
Vol 27 (03) ◽  
pp. 83-86 ◽  
Author(s):  
B. Briele ◽  
F. Wolf ◽  
H. J. Biersack ◽  
F. F. Knapp ◽  
A. Hotze

A prospective study was initiated to compare the clinically proven results concerning localization/extent and activity of inflammatory bowel diseases with those of 111ln-oxine leukocyte imaging. All patients studied were completely examined with barium enema x-ray, clinical and laboratory investigations, and endoscopy with histopathology. A total of 31 leukocyte scans were performed in 15 patients (12 with Crohn’s disease, 3 with ulcerative colitis). The scans were graded by comparing the cell uptake of a lesion (when present) and a bone marrow area providing a count ratio (CR). The inflammatory lesions were correctly localized on 26 leukocyte scans, and in 21 scans the scintigraphically estimated extent of disease was identical to endoscopy. In 5 cases the disease extent was underestimated, 4 scans in patients with relapse of Crohn’s disease were falsely negative, and in one patient with remission truly negative. The scintigraphically assessed disease activity was also in a good agreement with clinical disease activity based on histopathology in all cases. We conclude that leukocyte imaging provides valuable information about localization and activity of inflammatory bowel disease.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.


2021 ◽  
Vol 2021 (4) ◽  
Author(s):  
Leen Jamel Doya ◽  
Maria Naamah ◽  
Noura Karkamaz ◽  
Narmin Hajo ◽  
Fareeda Wasfy Bijow ◽  
...  

ABSTRACT Inflammatory bowel diseases (IBD) and Celiac disease (CeD) are immune-mediated gastrointestinal diseases with incompletely understood etiology. Both diseases show a multifactorial origin with a complex interplay between genetic, environmental factors, and some components of the commensal microbiota. The coexistence of celiac disease with Crohn’s disease is rarely reported in the literature. Here, we report a case of a 13-year-old Syrian male who presented with a history of abdominal pain, anorexia and pallor. CeD and Crohn’s disease was documented on gastrointestinal endoscopy and histological study. The patient was treated with a gluten-free, low fiber, high caloric diet, and a course of oral corticosteroids with an improvement in growth rate and abdominal pain.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Bruno Rafael Ramos de Mattos ◽  
Maellin Pereira Gracindo Garcia ◽  
Julia Bier Nogueira ◽  
Lisiery Negrini Paiatto ◽  
Cassia Galdino Albuquerque ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.


2021 ◽  
Vol 14 (3) ◽  
pp. e239404
Author(s):  
Clare Harris ◽  
Richard James Harris ◽  
Louise Downey ◽  
Markus Gwiggner

Active inflammatory bowel disease (IBD), combined immunosuppression and corticosteroid therapy have all been identified as risk factors for a poor outcome in COVID-19 infection. The management of patients with both COVID-19 infection and active IBD is therefore complex. We present the case of a 31-year-old patient with Crohn’s disease, on dual immunosuppression with infliximab and mercaptopurine presenting with inflammatory small bowel obstruction and COVID-19 infection. The case highlights the use of nutritional therapy, which remains underused in the management of adults with IBD, to manage his flare acutely. Following negative SARS-CoV-2 PCR testing and SARS-CoV-2 IgG testing confirming an antibody response, ustekinumab (anti-interleukin 12/23) was prescribed for long-term maintenance.


2014 ◽  
Vol 86 (9) ◽  
Author(s):  
Aneta Raczkowska ◽  
Michał Ławiński ◽  
Aleksandra Gradowska ◽  
Urszula Zielińska-Borkowska

AbstractOne of the elements of treatment considering inflammatory bowel diseases is nutritional therapy. The duration of the above-mentioned depends on the prevalence of such symptoms as fever, bowel move-ments, length of the functioning gastrointestinal tract, stoma and intestinal fistula presence. Nutritional therapy is an essential element of successful treatment alongside pharmacological, surgical, and biological therapy, as well as other methods. Crohn's disease and ulcerative colitis considered as chronic diseases, lead towards physical and biopsychosocial disability, being responsible for the reduction in the quality of life.was to determine the quality of life after surgical procedures in case of patients diagnosed with Crohn's disease and ulcerative colitis, subjected to natural and parenteral nutrition.The study group comprised 52 patients from the Department of Gastroen-terology, Military Medical Institute, and Department of Surgery and Clinical Nutrition, Clinical Hospital in Warsaw. The study was performed between October, 2011 and April, 2012. The World Health Organization Quality of Life Instrument - Bref (WHOQOL-BREF) questionnaire was used to deter-mine the patients’ quality of life.A lower quality of life was observed in case of patients subjected to parenteral nutrition, poor education, disease symptoms exacerbation, in the majority-rural inhabitants. The quality of life does not depend on gender, type of disease, family status, and additional medical care.


2018 ◽  
pp. 1-6
Author(s):  
Marwah Sami M Hussain ◽  
Bandar Idrees Ali ◽  
Abdullah Alzahrani

Background: Inflammatory bowel diseases are strongly associated with colorectal cancer. In addition, a few cases reported with gastric and small bowel adenocarcinoma in gastroduodenal Crohn’s disease. Case report: We reported a case of a 47-Year-old female, who was referred to our surgical department and after a routine gastroscopy which revealed a lesion. Biopsy confirmed gastric well-differentiated adenocarcinoma of limited gastric Crohn’s disease, for a patient on regular anti Crohn’s medication. The patient underwent varying laparoscopic distal gastrectomy. She received adjuvant chemotherapy treatment and thereafter, she was cancer free within the period of 3- years of regular follow up. Conclusion: The only way to diagnose such lesions of a rare case of gastric cancer in a patient with Crohn’s disease is to regularly carry out upper gastrointestinal examinations. Keywords: Inflammatory bowel diseases, Crohn’s disease, Upper gastrointestinal tract Crohn’s disease, Gastric cancer


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