Gastroenterology and Hepatology From Bed to Bench
Year:2015 | Volume:8 | Issue:2|Papers Count:13

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Individuals with particular genetic backgrounds develop immune responses to wheat proteins and become ‘gluten-sensitised’. Mucosal pathology arises through activated mucosal T lymphocytes, resulting in a graded, adverse reaction between particular genes and wheat proteins. Given these varied influences, the Marsh Classification broadly itemises those stages through which a normal mucosa (Marsh 0) evolves in becoming ‘flat’ (Marsh I, II, III).Recently, Oberhuber and colleagues suggested that Marsh III lesions required subdividing into a, b, c categories. We critically examined these subdivisions by means of correlative light and scanning electron microscopy (SEM). Our results demonstrate that Oberhuber’s classification is untenable. In our view deriving from our observations, the artificial subdivisions proposed by those authors actually reflect misinterpretations of the true architectural contours of flat mucosae. Although these workers refer to “villous projections”, SEM demonstrates that no such structures are present on flat - or immediately recovering–mucosae.Our data revealed on the surfaces of flat (Marsh III) mucosae, large open “basins”, surrounded by raised collars - the latter, when viewed in histological section, being easily misconstrued as “villi”. It seems that with subsequent upward growth, these collars coalesce into low ridges, thence becoming broader and higher convolutions. It is noticeable that there are more open spaces on the surfaces of flat mucosae than was appreciated hitherto. We conclude that Oberhuber’s revisions of Marsh III into three subcategories (a, b, c), are misinterpretations of the histological appearances of flattened mucosae. Therefore, histopathologists when classifying celiac mucosae, since they add nothing either of diagnostic, nor prognostic, value should resist these subcategories.

The diagnosis of Celiac Disease (CD) relies on the concordance of pathological, serological, genetic and clinical features. For this reason, the diagnosis of CD is often a challenge. Seronegative celiac disease (SNCD) is defined by the negativity of anti-tissue transglutaminase antibodies in the presence of a positive histology on duodenal biopsy samples, i.e. inflammatory infiltrate of intra-epithelial lymphocytes (IELs > 25/100 enterocytes), mild villous atrophy and uneven brush border associated to human leukocyte antigen (HLA) haplotype DQ2 and/or DQ8.SNCD is characterized by mucosal deposits of tissue transglutaminase (tTG)/anti-tTG immuno-complexes. These may counteract the passage of anti-tTG into the bloodstream, thus explaining seronegativity. Another reason for seronegativity may be found in an incomplete maturation of plasma cells with a consequent failure of antibodies production. This condition often characterizes immunoglobulin deficiencies, and, indeed, SNCD is common in subjects with immunoglobulin deficiencies.The management of SNCD still remains debated. The treatment option for SNCD may be represented by gluten free diet (GFD), but the usefulness and appropriateness of prescribing GFD are controversial. Some evidences support its use only in SNCD subjects showing CD clear clinical picture and compatible HLA status. The choice of GFD administration could be linked to an investigation able to diagnose SNCD in no doubt even if a reliable test is not currently available. On these bases, a test helping the diagnosis of SNCD is justifiable and desirable.

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten in genetically predisposed individuals who carry the HLA-DQ2 or -DQ8 alleles. The immune response is abnormal in celiac disease with small intestinal epithelial damage via CD8+CD4- intraepithelial lymphocytes. The etiology is multifactorial involving genetic and environmental factors, an abnormal immune response, and intestinal dysbiosis. The innate and acquired T-cell mediated immunity play important roles in the pathogenesis of this disease, particularly CD4+ Th17 cells, which have been shown to have critical functions in host defense against bacterial pathogens and in the inflammatory responses to deamidated gluten peptides. We review what is known about the interaction between immune system and intestinal microbiota in the pathogenesis of celiac disease.

Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestine and characterized by a multitude gastrointestinal (GI) and extra GI symptoms. IBD (including ulcerative colitis and Crohn’s disease) is a group of inflammatory conditions of the small intestine and colon. The etiology of IBD is unknown, but it may be related to instability in the intestinal microflora that leading to an immoderate inflammatory response to commensal microbiota. Irritable bowel syndrome (IBS) is a common, long-term condition of the digestive system. Bloating, diarrhoea and/or constipation are nonspecific symptoms of IBS. Various studies have shown that some intestinal parasites can effect on immune system of infected hosts and in some cases, they are able to modify and change the host’s immune responses, particularly in autoimmune disorders like celiac disease and IBD. The main objective of this review is to investigate the relationship between intestinal parasites and different inflammatory bowel disorders.

Aim: The present study aimed to study the immunological changes seen in the intestinal epithelium of the celiac patients could also be detected in the peripheral blood lymphocyte populations.Background: Celiac disease (CD) is a small bowel enteropathy caused by permanent wheat gluten intolerance. One of the earliest signs of CD is an increase in the numbers of the intestinal intraepithelial lymphocytes (iIEL).Patients and methods: In this case-control study, totally 13 untreated subjects with acceptable criteria for CD without any complication and 16 healthy subjects without any positive criteria for CD were selected. Peripheral blood T cells were analyzed by two-color flow cytometry in both groups.Results: The mean age of patients was 33.6±3.4 years and two patients had Marsh IIIB, five patients had Marsh IIIA and six patients had Marsh II histology class. The mean percentages of the gdTCR+ T cells in the patients were significantly higher than the controls (p=0.015). However, the mean percentages of the abTCR+ T cells were significantly lower in the untreated patients than the controls (p=0.025). There were no significant difference between the mean percentages of lymphocytes expressing the CD3, CD4 and CD8 molecules in the patients and the controls.Conclusion: The change in the percentages of the peripheral blood T cells expressing the gdTCR and abTCR in the celiac patients could be used in conjunction with the other serological markers to identify new CD cases.

Aim: the aim of this study was to investigate the necessity of screening for celiac disease in idiopathic osteoporotic patients.Background: Osteopenia and osteoporosis are well-known and prevalent complications of celiac disease. However, the relative prevalence of celiac disease among osteoporotic populations is not known, and the benefit of screening for celiac disease among the osteoporotic population remains controversial.Patients and methods: We evaluated a total of 560 individuals, 460 with osteoporosis and 100 healthy subjects, from the rheumatology clinic in Imam Khomeini and Shariati hospital by IgA anti-tissue transglutaminase (anti-tTG) for celiac disease. Then individuals with positive serologic test underwent upper GI Endoscopy & 2nd part duodenum biopsies. The clinical findings were evaluated in both groups and were compared with each other.Results: Five (1.08%) of 460 patients with osteoporosis and 1 (1%) of 100 subjects without osteoporosis had celiac disease by positive serologic & pathology results. Three patients with positive serology & pathology results were female. All patients in osteoporotic group had at least one other symptom of celiac disease. Two of them had anemia and others had chronic abdominal pain, recurrent oral aphtous lesion & chronic bloating.Conclusion: In the present study, the prevalence of celiac disease in osteoporotic patients is not high enough to justify recommendation for serologic screening of celiac disease in all patients with idiopathic osteoporosis; but in osteoporotic patients with other celiac or gastrointestinal symptoms and signs, for example iron deficiency anemia, chronic dyspepsia and bloating, constipation or diarrhea and recurrent aphtous lesions, it is necessary to evaluate for celiac disease.

Aim: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients.Background: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations.Patients and methods: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections.Results: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P<0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively.Conclusion: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively.

Aim: This study reports evaluated prevalence of CD in patients with Beta-thalassemia major.Background: Celiac Disease (CD) is an autoimmune disorder triggered by ingestion of gluten in genetically predisposed individuals.Patients and methods: In this case-control study in a period of 3 years, which was performed on 620 children in two groups of Beta-thalassemia major patients (n=200) and control (n=420), serum tissue transglutamianse (tTG) IgA levels were measured. The two groups were compared together in terms of tTG IgA levels, and p<0.05 was considered significant.Results: The means of serum tTG IgA levels in patients with Beta-thalassemia major and control groups were 28.81±68.44 and 6.94±6.68 U/mL, respectively. There was a significant difference in favor of the case group (p=0.000). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001). Belonging to each group will change the probability of having less than 20 in tTG IgA (odds=0.285) and it means that belonging to the control group has a protective role. There is only a significant association in the case of all population (r=0.102, p=0.011). Body mass index in the two case and control groups had a significant difference (t=3.859, p=0.001).Conclusion: Probability of CD should be considered since the prevalence of CD is high in patients with and Beta-thalassemia major. Patients with thalassemia major are recommended for screening for CD.

Aim: This study was aimed to evaluate symptomatic as well as histopathologic response to GFD in patients with gluten-sensitive enteropathies including celiac disease, lymphocytic duodenosis and non-specific duodenitis.Background: Gluten-free diet (GFD) is the main treatment of celiac disease. However, its impact on other disorders of gluten sensitivity spectrum is less clear.Patients and methods: In a prospective observational study in Modarres hospital Tehran, Iran, 35 patients with chronic manifestations including low BMI, diarrhea, greasy stool and bloating were evaluated using serology for anti-tTG, endoscopy and histopathology. Patients were categorized in three diagnostic groups accordingly including celiac disease (CD), lymphocytic doudenosis (LD) and non-specific duodenitis (NSD). All patients were put on a GFD for 6 months, and subjective symptomatic response, serology, endoscopy and histopathologic tests were repeated and compared with baselines and among groups.Results: Of the total 35 patients, 5 had CD (14.3%), 9 had LD (25.7%) and 21 (60%) had NSD. Bloating was the most common symptom followed by diarrhea. Majority of patients (80%) had low BMI. All symptoms alleviated following a GFD but bloating was the only significant one. A significant increase was found in total mean BMI (17.3±0.7 v.s. 17.9±0.9). Histopathologic examination showed a complete resolution in 48.5% (n=17) patients, 10 in NSD group, 4 in LD group and 3 in CD group. Final prevalence of gluten-sensitive enteropathy (LD and NSD cases that responded to GFD) was 46.6%.Conclusion: GFD may have more implications other than celiac disease. Other gluten-sensitive enteropathies, like LD and NSD, might also respond to this treatment particularly in patients with low BMI.

Constipation is the most common digestive complaint in the general population. It is associated with considerable adverse effect on quality of life and substantial economic costs and often has no underlying pathology. Non-Celiac Gluten Sensitivity (NCGS) has been described as a cause of constipation in a few studies. We present a 62-year-old male with long standing constipation without any underlying cause during extensive surveys and not responding to any conservative treatment but significant response with gluten free diet (GFD).

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