Linking Genetic Diagnosis to Therapeutic Approach in Very Early Onset Inflammatory Bowel Disease: Pharmacologic Considerations

Levine, Anne E.; Zheng, Hengqi; Suskind, David L.

doi:10.1007/s40272-022-00503-4

Cited by 5 publications

(4 citation statements)

References 94 publications

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“…Классификация основных вариантов первичных иммунодефицитных состояний, ассоциированных с ВЗК-подобными проявлениями, с верифицированными генетическими вариантами [7,15,16,18] Варианты Для лечения пациентов с ПИДС помимо симптоматической, антибактериальной и противогрибковой терапии используют заместительную терапию иммуноглобулинами, лечение генно-инженерно-биологическими препаратами и таргетными иммуносупрессивными средствами; кроме этого, важной терапевтической опцией является трансплантация гемопоэтических стволовых клеток [25,26]. При некоторых вариантах ПИДС проведение трансплантации стволовых гемопоэтических клеток позволяет улучшить качество жизни и увеличить ее продолжительность, в большинстве случаев приводит к достижению стойкой ремиссии заболевания и даже выздоровлению [27].…”

Section: эпидемиология и классификация первичных иммунодефицитных сос...unclassified

Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis

Shcherbakova

2024

Almanac of Clinical Medicine

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From the beginning of 2000s, there has been a significant increase in the incidence of inflammatory bowel diseases (IBD) and primary immunodeficiency disorders (PIDs) in adults and children in many countries around the world. The aim of the review is to summarize the state-of-the-art on diverse clinical types of PIDs with gastrointestinal manifestations and their differential diagnostic algorithms. Atypical PIDs with “blunted” clinical manifestations are challenging for the timely diagnosis. Some types of PIDs with gastrointestinal involvement are also difficult to differentiate with classical IBDs. Molecular genetic studies have allowed for selection of a specific group of monogenic IBD-like diseases, represented mainly by PIDs. The authors discuss current classification of PIDs and their main clinical types imitating IBD, with important clinical and laboratory aspects. High level of information and awareness of practicing specialists working with IBD patients would be helpful in the selection of a patient cohort with possible PIDs and in the performance of extended laboratory assessment or referring for genetic tests. Timely diagnosis of PIDs would ensure quick administration of target therapy or hematopoietic stem cell transplantation, which in most cases would allow for the achievement of the disease remission, improvement of quality and duration of life.

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Section: эпидемиология и классификация первичных иммунодефицитных сос...unclassified

Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis

Shcherbakova

2024

Almanac of Clinical Medicine

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“…Currently, over 100 disease-associated genes have been identified [ 1 , 7 , 8 ]. Causative immunodeficiencies can be classified as epithelial cell defects, phagocytic defects, defects of adaptive immunity, T regulatory defects, IL-10 pathway disorders, and hyperinflammatory or autoinflammatory conditions [ 3 , 9 , 10 , 11 , 12 ] ( Table 1 ). Monogenic defects of the epithelium often involve the gut and the skin due to shared embryologic precursors.…”

Section: Monogenic Inflammatory Bowel Diseasesmentioning

confidence: 99%

“…CTLA4 is an inhibitory immune checkpoint protein that is expressed on FOXP3+ T-regulatory cells. Abatacept is used as a targeted therapy for LRBA deficiency, which is marked by very low CTLA4 expression and presents with enteropathy and other systemic manifestations [ 3 , 11 , 12 , 132 ]. In a study of 22 children with LRBA deficiency who were treated with abatacept, 11 achieved complete remission, and three had partial remission.…”

Section: Targeted Therapies For Monogenic Ibdmentioning

confidence: 99%

Pharmacologic Management of Monogenic and Very Early Onset Inflammatory Bowel Diseases

et al. 2023

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Inflammatory bowel disease (IBD) is treated with a variety of immunomodulating and immunosuppressive therapies; however, for the majority of cases, these therapies are not targeted for specific disease phenotypes. Monogenic IBD with causative genetic defect is the exception and represents a disease cohort where precision therapeutics can be applied. With the advent of rapid genetic sequencing platforms, these monogenic immunodeficiencies that cause inflammatory bowel disease are increasingly being identified. This subpopulation of IBD called very early onset inflammatory bowel disease (VEO-IBD) is defined by an age of onset of less than six years of age. Twenty percent of VEO-IBDs have an identifiable monogenic defect. The culprit genes are often involved in pro-inflammatory immune pathways, which represent potential avenues for targeted pharmacologic treatments. This review will provide an overview of the current state of disease-specific targeted therapies, as well as empiric treatment for undifferentiated causes of VEO-IBD.

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“…VEO-IBD associated monogenic variants are classified into 5 distinct groups: 1) Epithelial barrier defects; 2) Phagocytic defects; 3) T and B cell defects; 4) T regulatory cells and signaling defects; and 5) Hyper-and auto-inflammatory conditions [1,[5][6][7] (Figure 1). Identifying a monogenic etiology of VEO-IBD can have significant impact on treatment regimens, as specific immunological mechanisms can be targeted [1,6,[8][9][10]. Based on a 2020 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) position paper on VEO-IBD, recommendations of clinical approach and diagnostic strategies have shifted in the past year [9].…”

Section: Introductionmentioning

confidence: 99%

Evolving a Single Institution’s Approach to Very Early Onset Inflammatory Bowel Disease (VEO-IBD) through Literature Review and Collaborative Efforts

2024

J Community Med Public Health

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Objective: Very Early Onset Inflammatory Bowel Disease (VEO-IBD) is defined as a diagnosis of IBD before 6 years of age. VEO-IBD often follows a more recalcitrant disease course and can be associated with underlying Inborn Errors of Immunity (IEI). Methods: We describe our single institution experience in caring for patients with VEO-IBD as a tertiary referral center for pediatric IBD, how we utilized this most recent literature review to provide self-assessment in workup, and how we transformed our approach to VEO-IBD care through collaboration, using a stepwise laboratory and clinical paradigm for this vulnerable cohort of IBD patients. Results: A retrospective review of 34 patients was performed with description of clinical phenotypes, tissue pathology, clinical management and outcomes. The majority of our VEO-IBD patients presented with colonic Crohn's disease. A high percentage of patients were refractory to anti-Tumor Necrosis Factor (TNF) therapy. Only 26/34 (76%) of our VEO-IBD patients had any immunological testing done and genetic testing was performed on only 5/34 patients (15%). Discussions: Our review process identified a need for expedited standardized immune workup for this population at our institution. Based upon this introspective work, an algorithm for immunological and genetic evaluation at time of diagnosis was developed, aimed at creating a multi-disciplinary approach for the comprehensive evaluation of this at-risk patient population.

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Linking Genetic Diagnosis to Therapeutic Approach in Very Early Onset Inflammatory Bowel Disease: Pharmacologic Considerations

Cited by 5 publications

References 94 publications

Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis

Primary immunodeficiency disorders imitating inflammatory bowel diseases: clinical aspects and problems of the differential diagnosis

Pharmacologic Management of Monogenic and Very Early Onset Inflammatory Bowel Diseases

Evolving a Single Institution’s Approach to Very Early Onset Inflammatory Bowel Disease (VEO-IBD) through Literature Review and Collaborative Efforts

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