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GE Portuguese Journal of... Mar 2022Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy... (Review)
Review
Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.
PubMed: 35497669
DOI: 10.1159/000514716 -
Nutrients Nov 2018Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and... (Review)
Review
Recently, the interest in the human microbiome and its interplay with the host has exploded and provided new insights on its role in conferring host protection and regulating host physiology, including the correct development of immunity. However, in the presence of microbial imbalance and particular genetic settings, the microbiome may contribute to the dysfunction of host metabolism and physiology, leading to pathogenesis and/or the progression of several diseases. Celiac disease (CD) is a chronic autoimmune enteropathy triggered by dietary gluten exposure in genetically predisposed individuals. Despite ascertaining that gluten is the trigger in CD, evidence has indicated that intestinal microbiota is somehow involved in the pathogenesis, progression, and clinical presentation of CD. Indeed, several studies have reported imbalances in the intestinal microbiota of patients with CD that are mainly characterized by an increased abundance of spp. and a decrease in spp. The evidence that some of these microbial imbalances still persist in spite of a strict gluten-free diet and that celiac patients suffering from persistent gastrointestinal symptoms have a desert gut microbiota composition further support its close link with CD. All of this evidence gives rise to the hypothesis that probiotics might play a role in this condition. In this review, we describe the recent scientific evidences linking the gut microbiota in CD, starting from the possible role of microbes in CD pathogenesis, the attempt to define a microbial signature of disease, the effect of a gluten-free diet and host genetic assets regarding microbial composition to end in the exploration of the proof of concept of probiotic use in animal models to the most recent clinical application of selected probiotic strains.
Topics: Animals; Bacteria; Celiac Disease; Diet, Gluten-Free; Dysbiosis; Gastrointestinal Microbiome; Humans; Probiotics
PubMed: 30477107
DOI: 10.3390/nu10121824 -
Journal of Autoimmunity Mar 2021Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to... (Review)
Review
Immune-mediated enteropathies are caused by excessive reactions of the intestinal immune system towards non-pathogenic molecules. Enteropathy leads to malabsorption-related symptoms and include (severe) chronic diarrhea, weight loss and vitamin deficiencies. Parenteral feeding and immunosuppressive therapy are needed in severe cases. Celiac disease has long been recognized as the most common immune-mediated enteropathy in adults, but the spectrum of immune-mediated enteropathies has been expanding. Histological and clinical features are sometimes shared among these enteropathies, and therefore it may be challenging to differentiate between them. Here, we provide an overview of immune-mediated enteropathies focused on clinical presentation, establishing diagnosis, immunopathogenesis, and treatment options.
Topics: Animals; Clinical Trials as Topic; Disease Models, Animal; Humans; Immune System Diseases; Immunity, Mucosal; Immunosuppression Therapy; Intestinal Diseases; Intestinal Mucosa; Parenteral Nutrition; Treatment Outcome
PubMed: 33607573
DOI: 10.1016/j.jaut.2021.102609 -
Middle East Journal of Digestive... Oct 2020Celiac disease (CeD) is a widespread autoimmune enteropathy caused by dietary gluten peptides in genetically susceptible individuals, which includes a range of... (Review)
Review
Celiac disease (CeD) is a widespread autoimmune enteropathy caused by dietary gluten peptides in genetically susceptible individuals, which includes a range of intestinal and extraintestinal manifestations. Currently, there is no effective treatment for CeD other than strict adherence to a gluten-free diet (GFD). However, persistent or frequent symptoms and also partial villus atrophy were observed in some patients with CeD due to intentional or inadvertent gluten exposure during the use of GFD. It means that GFD alone is not enough to control CeD symptoms and long-term complications. Accordingly, new therapeutic approaches for CeD treatment such as gluten proteolysis, removing gluten from the digestive tract, promoting tight junction assembly, inhibiting intestinal tissue transglutaminase 2, using probiotics, and developing immunotherapeutic methods have been proposed through different strategies. This review focused on discussing the novel therapeutic strategies for CeD management.
PubMed: 33564379
DOI: 10.34172/mejdd.2020.187 -
Clinical and Experimental Immunology Jul 2021Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified... (Review)
Review
Cytotoxic T lymphocyte antigen 4 (CTLA-4) haploinsufficiency (CHAI) and lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life-threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9 B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre- and post-transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
Topics: Adaptor Proteins, Signal Transducing; CTLA-4 Antigen; Haploinsufficiency; Humans; Immunoglobulins; Immunosuppressive Agents; Lymphocytes
PubMed: 33788257
DOI: 10.1111/cei.13600 -
Current Gastroenterology Reports Oct 2012Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary... (Review)
Review
Autoimmune enteropathy (AIE) is a rare condition characterized by intractable diarrhea, histologic changes on small intestinal biopsy, and failed response to dietary manipulation that also may present with extraintestinal manifestations. In many patients, immunosuppressive therapies are necessary. Although AIE is more common in infants, adult involvement has also been documented. Much of what is known about AIE has been gathered from case reports and small case series; therefore, more research in this evolving field is needed. IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome) and APECED (autoimmune phenomena, polyendocrinopathy, candidiasis, and ectodermal dystrophy) are systemic forms of AIE.
Topics: Adult; Autoimmune Diseases; Humans; Immunosuppressive Agents; Infant; Intestinal Diseases; Parenteral Nutrition
PubMed: 22810979
DOI: 10.1007/s11894-012-0276-2 -
World Journal of Gastroenterology Feb 2008Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and...
Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti-enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.
Topics: Adult; Autoantibodies; Autoimmune Diseases; Celiac Disease; Enterocytes; Gastroenterology; Goblet Cells; Humans; Stomach Diseases
PubMed: 18300339
DOI: 10.3748/wjg.14.1156 -
Acta Bio-medica : Atenei Parmensis Dec 2022Celiac disease is an autoimmune enteropathy of the small intestine, related to gluten intolerance occurring in genetically predisposed patients. Currently, the only... (Review)
Review
Celiac disease is an autoimmune enteropathy of the small intestine, related to gluten intolerance occurring in genetically predisposed patients. Currently, the only available treatment is a lifelong gluten-free diet. However, the total avoidance of gluten is difficult and poses a challenge to patients, nutritionists and treating physicians. For this reason, scientists have developed in recent years new therapeutic approaches complementary to dietary treatment, such as modification of gluten to make gliadin non-toxic, reduction of the inflammatory response with elafin and Lactococcus Lactis, degradation of gluten by endoproteolytic enzymes, and correction of nutritional deficiencies by adding pseudo-cereals to the diet of celiac patients. This literature review focuses on the different treatment strategies for celiac disease previously studied and summarizes the latest advances in this field.
Topics: Humans; Celiac Disease; Diet, Gluten-Free; Glutens; Intestine, Small; Malnutrition
PubMed: 36533746
DOI: 10.23750/abm.v93i6.13673 -
Pathologica Feb 2022The gastrointestinal (GI) tract may be involved in systemic autoimmune diseases or may be the target of organ-specific autoimmunity. Autoimmune enteropathy (AIE) is a... (Review)
Review
The gastrointestinal (GI) tract may be involved in systemic autoimmune diseases or may be the target of organ-specific autoimmunity. Autoimmune enteropathy (AIE) is a rare disorder characterized by severe and protracted diarrhea, weight loss from malabsorption and immune-mediated damage to the intestinal mucosa, generally occurring in infants and young children, only rarely in adult. The salient histopathologic features of AIE are most prominent in the small intestine: villous blunting, crypt hyperplasia, mononuclear cell inflammatory expansion of the lamina propria with intraepithelial lymphocytosis, crypt apoptosis and absence of Paneth cells, goblet cells or both. Esophagus, stomach and colon are frequently also involved. Anti-enterocyte antibodies are identified in the majority of cases, and their presence, even if variable, can help confirming the diagnosis. The purpose of this review is to provide an overview of the latest immunological advances in AIE, as well as to offer a practical approach for histological diagnosis for 'general' pathologist.
Topics: Autoimmune Diseases; Child; Child, Preschool; Gastrointestinal Tract; Humans; Intestinal Mucosa; Intestine, Small; Polyendocrinopathies, Autoimmune
PubMed: 34856606
DOI: 10.32074/1591-951X-339 -
Frontiers in Cellular Neuroscience 2022Enteric glial cells (EGCs) are one of the major cell types of neural crest lineage distributed in the gastrointestinal tract. EGCs represent an integral part of the... (Review)
Review
Enteric glial cells (EGCs) are one of the major cell types of neural crest lineage distributed in the gastrointestinal tract. EGCs represent an integral part of the enteric nervous system (ENS) and significantly outnumber ENS neurons. Studies have suggested that EGCs would exert essential roles in supporting the survival and functions of the ENS neurons. Notably, recent evidence has begun to reveal that EGCs could possess multiple immune functions and thereby may participate in the immune homeostasis of the gut. In this review article, we will summarize the current evidence supporting the potential involvement of EGCs in several important immunological disorders, including inflammatory bowel disease, celiac disease, and autoimmune enteropathy. Further, we highlight critical questions on the immunological aspects of EGCs that warrant future research attention.
PubMed: 35573829
DOI: 10.3389/fncel.2022.895871