scholarly journals Phenotype and genotype characteristics of neonatal onset inflammatory bowel disease with combined immunodeficiency of TTC7A deficiency in mainland China

2021 ◽  
Author(s):  
Yun e Chen ◽  
Jing fang Chen ◽  
Wen xing Guo ◽  
Yan hong Zhang ◽  
Jia ling Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mainland China ◽  
Clinical Manifestations ◽  
Compound Heterozygote ◽  
Immune Functions ◽  
Combined Immunodeficiency ◽  
Histological Findings ◽  
Neonatal Onset ◽  
Inflammatory Bowel

Abstract Objective: To explore the characteristics of genotype and phenotype of neonatal onset inflammatory bowel disease with combined immunodeficiency caused by a novel TTC7A mutant. Methods: We summarized the clinical manifestations, imagings, endoscopic and histological findings, biochemical analyses,whole exon sequencing(WES), in silico and intervention of the patient. Results: The boy showed severe diarrhea, malnutrition, electrolyte disturbance, dehydration and recurrent infections after birth. X-ray and ultrasonic images displayed no specific changes. Endoscopic and histological findings showed chronic inflammation. Immune functions indicated combined immunodeficiency. WES identified compound heterozygote TTC7A mutations c.2355+4A>G/c.643G>T in the infant. No abnormal splicing sequence by c.2355+4A>G mutation was found in TTC7A expression analysis, but the mRNA expression decreased. There was no improvement after treatment with methylprednisolone and leflunomide. The infant died when he was given up at 5 months 19 days old. Conclusion: The compound heterozygote mutations (c.2355+4A>G, c.643G>T) in TTC7A gene were firstly described and confirmed. Our report expands the phenotypic spectrum of TTC7A mutaions and genotypic spectrum of very early onset inflammatory bowel disease with combined immunodeficiency.

Role of Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Sara Lovisa ◽  
Giannicola Genovese ◽  
Silvio Danese
Keyword(s):  
Inflammatory Bowel Disease ◽  
Wound Healing ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Clinical Manifestations ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
Inflammatory Bowel

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.

scholarly journals Anemia in Crohn’s Disease—The Unseen Face of Inflammatory Bowel Disease

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1046
Author(s):  
Mihaela Dranga ◽  
Lucian Vasile Boiculese ◽  
Iolanda Popa ◽  
Mariana Floria ◽  
Oana Gavril ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Clinical Manifestations ◽  
World Health ◽  
Tertiary Center ◽  
Inflammatory Bowel ◽  
The Impact

Background and Objectives: Anemia is the most frequent complication of inflammatory bowel diseases. Clinically, anemia can affect important quality-of-life (QoL) components, such as exercise capacity, cognitive function, and the ability to carry out social activities. The disease activity has a significant impact on QoL, mainly due to clinical manifestations, which are more severe during the periods of disease activity. Our aim was to estimate the impact of anemia on QoL in patients with Crohn’s disease. Material and Methods. We made a prospective study on 134 patients with Crohn’s disease (CD) in a Romanian tertiary center. The CD diagnosis was established by colonoscopy and histopathological examination. In particular cases, additional examinations were required (small bowel capsule endoscopy, computed tomography enterography, and magnetic resonance enterography). Anemia was defined according to the World Health Organization’s definition, the activity of the disease was assessed by Crohn’s disease activity index (CDAI) score, and the QoL was evaluated by Inflammatory Bowel Disease Questionnaire 32 (IBDQ 32). Results: 44.8% patient had anemia, statistically related to the activity of the disease and corticoids use. We found a strong association between QoL and disease activity on all four sub-scores: patients with more severe activity had a significantly lower IBDQ (260.38 ± 116.96 vs. 163.85 ± 87.20, p = 0.001) and the presence of anemia (127.03 vs. 148.38, p = 0.001). In multiple regression analyses, both disease activity and anemia had an impact on the QoL. Conclusions: Anemia has high prevalence in the CD in northeastern region of Romania. Anemia was more common in female patients, in patients undergoing corticosteroid treatment, and in those with active disease. Both anemia and disease activity had a strong negative and independent impact on QoL.

scholarly journals THE ONSET OF CLINICAL MANIFESTATIONS IN INFLAMMATORY BOWEL DISEASE PATIENTS

2018 ◽  
Vol 55 (3) ◽  
pp. 290-295
Author(s):  
Viviane Gomes NÓBREGA ◽  
Isaac Neri de Novais SILVA ◽  
Beatriz Silva BRITO ◽  
Juliana SILVA ◽  
Maria Carolina Martins da SILVA ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Clinical Manifestations ◽  
Inflammatory Bowel ◽  
The Mean ◽  
Mean Time

ABSTRACT BACKGROUND: The diagnosis of inflammatory bowel disease is often delayed because of the lack of an ability to recognize its major clinical manifestations. OBJECTIVE: Our study aimed to describe the onset of clinical manifestations in inflammatory bowel disease patients. METHODS: A cross-sectional study. Investigators obtained data from interviews and the medical records of inflammatory bowel disease patients from a reference centre located in Brazil. RESULTS: A total of 306 patients were included. The mean time between onset of symptoms and diagnosis was 28 months for Crohn’s disease and 19 months for ulcerative colitis. The main clinical manifestations in Crohn’s disease patients were weight loss, abdominal pain, diarrhoea and asthenia. The most relevant symptoms in ulcerative colitis patients were blood in the stool, faecal urgency, diarrhoea, mucus in the stool, weight loss, abdominal pain and asthenia. It was observed that weight loss, abdominal pain and distension, asthenia, appetite loss, anaemia, insomnia, fever, nausea, perianal disease, extraintestinal manifestation, oral thrush, vomiting and abdominal mass were more frequent in Crohn’s patients than in ulcerative colitis patients. The frequencies of urgency, faecal incontinence, faeces with mucus and blood, tenesmus and constipation were higher in ulcerative colitis patients than in Crohn’s disease patients. The mean time from the onset of clinical symptoms to the diagnosis of Crohn’s disease was 37 months for patients with ileocolonic location, 26 months for patients with ileum location and 18 months for patients with colon location. In ulcerative colitis patients, the mean time from the onset of symptoms to diagnosis was 52 months for proctitis, 12 months for left-sided colitis and 12 months for extensive colitis. CONCLUSION: Ulcerative colitis presented a high frequency of intestinal symptoms, and Crohn’s disease showed a high frequency of systemic manifestations at the onset of manifestation. There was a long delay in diagnosis, but individuals with more extensive disease and more obvious symptoms showed a shorter delay.

scholarly journals Overview of Inflammatory Bowel Disease Pathogenesis

1990 ◽  
Vol 4 (7) ◽  
pp. 309-316 ◽  
Author(s):  
C Fiocchi
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Antigen Processing ◽  
Inflammatory Responses ◽  
Clinical Manifestations ◽  
Intestinal Immunity ◽  
Primary Defect ◽  
Ulcer Disease ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD) represents a difficult and challenging condition for patients, clinicians and basic investigators alike. Its etiology and pathogenesis are still unclear in spite of extensive investigations that have yielded a wealth of clinical. epidemiological, biochemical, bacteriological and immunological data on Crohn 's disease and ulcerative colitis. Although the precise mechanism(s) responsible for the intestinal inflammatory process remain to be defined, enough information has been assembled to hypothesize which components are likely to be important for this probably multifactorial disease. A consistent association between class I or II histocompatibility antigens and either Crohn's disease or ulcerative colitis has yet to be found. Nevertheless, ample epidemiological studies leave no doubt about the high frequency of familial clustering, and it must be determined whether this phenomenon translates a true genetic predisposition or a common environmental exposure, or both. Immune events occurring in the gastrointestinal tract are unquestionably linked to the pathogenesis of IBD, but it is unknown which are primary or secondary in nature. While most immune abnormalities detected in patients with established disease are likely to represent secondary events, these are no less important, as they probably contribute to the perpetuation of gut inflammation and tissue damage. This does not exclude that IBD is due to a primary defect of intestinal immunity, but this may no longer be detectable at the time of clinical manifestations. The answer to the question of wh1ch of the various intestinal immune abnormalities is central to pathogenesis must wait for additional research. Whether immune responses to the luminal flora, antigen processing mechanisms, antibody production, immunoregulation, cytotoxic activity, cytokine and mediator release are defective or disregulated is under intense investigation. It is likely that several of these events are involved, but they may interact in a complex and unpredictable fashion. lt is almost certain that there are various initiating and secondary events, and different immune mechanisms share relatively few common pathways for damaging the intestine, eg, cytokines, arachidonic acid metabolites, and oxidants. Perseverance in the study of these substances is finally yielding promising new approaches to the manipulation of immune and inflammatory responses chat cause bowel destruction. Future drugs may consist of combinations of highly specific inhibitors, antagonists or receptor blockers, that may selectively block one or several steps of the inflammatory cascade which is chronically active in the intestine of affected individuals. Therefore, we may soon face a situation not too dissimilar from what we have recently witnessed for peptic ulcer disease. The specific cause of IBD may still be beyond our comprehension, but a better understanding of its pathogenesis al lows us to put highly effective therapies within reach.

scholarly journals P754 Inflammatory bowel disease-like disease in patients with primary immunodeficiencies with chronic digestive symptoms: Diagnostic yield of colonoscopy

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S602-S603
Author(s):  
M B SANCHEZ ◽  
J Cepeda ◽  
M J Etchevers ◽  
M J Sobrero ◽  
R Gonzalez Sueyro ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Plasma Cells ◽  
Diagnostic Yield ◽  
Intraepithelial Lymphocytes ◽  
Primary Immunodeficiencies ◽  
Histological Findings ◽  
Histological Features ◽  
Selective Iga Deficiency ◽  
Inflammatory Bowel

Abstract Background Primary immunodeficiencies (PIDs) are a heterogeneous group of diseases characterised by genetic defects in the immune system. The respiratory and gastrointestinal tracts are the most affected. Digestive involvement may be due to infections, immune-mediation or malignancy. Immune-mediated involvement is expressed clinically and endoscopically like an inflammatory bowel disease (IBD-like disease). The objective of this study was to describe the endoscopic and histological findings in patients with PID and chronic digestive symptoms studied by colonoscopy with a final diagnosis of IBD-like disease. Methods Between 2004 and 2017 we included 30 patients with PID, chronic digestive manifestations and at least one colonoscopy with negative stool microbiological studies. Results Of the patients included, 19 (63%) were women. The median age was 62 years (IQR 49–74). Seven (23%) presented selective IgA deficiency, 11 (37%) common variable immunodeficiency (CVID) and 12 (40%) hypogammaglobulinemia. The digestive symptoms reported were chronic diarrhea (73%), abdominal pain (73%) and weight loss (36%). Ten patients (33.3%) had IBD associated, 5 had a pattern of ulcerative colitis (UC), 3 of Crohn’s disease (CD) and 2 of non-classifiable IBD (NCIBD). Diarrhoea was the most common manifestation in those with IBD-like disease (100%). The most frequent-related PID was CVID (54%). Of the 5 UC-like patients, 4 were extensive and 1 proctitis; the 3 CD-like patients presented ileocolic location. Of the 10 patients with IBD-like disease colonoscopy showed: oedema (40%), loss of vascular pattern (40%), erosions (30%), ulcers (40%), pseudopolyps (10%) and 50% did not present endoscopic findings at the time of the study. Histological features were chronic inflammation (100%), cryptitis-pericryptitis-microabscesses (60%) and granulomas (10%). Additionally, we found the presence of apoptotic cells (40%) and absence of plasmocytes in the lamina propria (40%). Upper endoscopy was performed concomitantly in 24 patients, in 17% we found at duodenum nodularity and scalloping. Duodenal biopsies were taken in 15 patients and the histological features were: increased intraepithelial lymphocytes (40%), crypt hyperplasia (20%), atrophic mucosa (6.6%). Conclusion One third of patients with PID and chronic digestive symptoms who performed a colonoscopy presented IBD-like disease. CVID was the most associated PID with IBD-like disease. Half of the patients had no colonoscopic findings, so taking random biopsies is suggested. Histological findings were typical of IBD, being the presence of apoptotic bodies and the absence of plasma cells distinctive of the associated PID.

scholarly journals LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency

2012 ◽  
Vol 130 (2) ◽  
pp. 481-488.e2 ◽  
Author(s):  
Abdullah Alangari ◽  
Abdulrahman Alsultan ◽  
Nouran Adly ◽  
Michel J. Massaad ◽  
Iram Shakir Kiani ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gene Mutation ◽  
Bowel Disease ◽  
Combined Immunodeficiency ◽  
Inflammatory Bowel

scholarly journals Selenium and inflammatory bowel disease

2015 ◽  
Vol 309 (2) ◽  
pp. G71-G77 ◽  
Author(s):  
Avinash K. Kudva ◽  
Ashley E. Shay ◽  
K. Sandeep Prabhu
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Microbiome ◽  
Bioactive Metabolites ◽  
Unknown Etiology ◽  
Regulation Of Transcription ◽  
Inverse Association ◽  
Immune Functions ◽  
Altered Expression ◽  
Inflammatory Bowel

Dietary intake of the micronutrient selenium is essential for normal immune functions. Selenium is cotranslationally incorporated as the 21st amino acid, selenocysteine, into selenoproteins that function to modulate pathways involved in inflammation. Epidemiological studies have suggested an inverse association between selenium levels and inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis that can potentially progress to colon cancer. However, the underlying mechanisms are not well understood. Here we summarize the current literature on the pathophysiology of IBD, which is multifactorial in origin with unknown etiology. We have focused on a few selenoproteins that mediate gastrointestinal inflammation and activate the host immune response, wherein macrophages play a pivotal role. Changes in cellular oxidative state coupled with altered expression of selenoproteins in macrophages drive the switch from a proinflammatory phenotype to an anti-inflammatory phenotype to efficiently resolve inflammation in the gut and restore epithelial barrier integrity. Such a phenotypic plasticity is accompanied by changes in cytokines, chemokines, and bioactive metabolites, including eicosanoids that not only mitigate inflammation but also partake in restoring gut homeostasis through diverse pathways involving differential regulation of transcription factors such as nuclear factor-κB and peroxisome proliferator-activated receptor-γ. The role of the intestinal microbiome in modulating inflammation and aiding in selenium-dependent resolution of gut injury is highlighted to provide novel insights into the beneficial effects of selenium in IBD.

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