Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease

Das, Prasenjit; Gahlot, Gaurav Pratap Singh; Mehta, Ritu; Makharia, Archita; Verma, Anil K.; Sreenivas, Vishnubhatla; Panda, Subrat Kumar; Ahuja, Vineet; Gupta, Siddhartha Datta; Makharia, Govind

doi:10.1016/j.dld.2016.06.013

Cited by 10 publications

(5 citation statements)

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“…These abnormal enterocyte features are presumably caused by the inflammatory response in CD. The changes may preface cell death, and indeed, increased small intestinal enterocyte apoptosis has been demonstrated in CD in several studies ( 40 , 57 , 58 ). Using TUNEL staining to detect fragmented DNA, Moss et al reported this finding in patients with untreated CD, and evidence of apoptosis correlated with the level of enterocyte proliferation ( 57 ).…”

Section: The Enterocyte—a Target Cell In Cd?mentioning

confidence: 92%

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

et al. 2020

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Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease.

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Section: The Enterocyte—a Target Cell In Cd?mentioning

confidence: 92%

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

et al. 2020

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“…A higher level of I‐FABP has been reported in blood of patients with CeD . Because the regenerative activity of enterocytes increases in enteropathic conditions including CeD, the regenerative activity in the crypts can be assessed by studying the expression of Reg1α gene and protein …”

Section: Introductionmentioning

confidence: 99%

“…29,30 Because the regenerative activity of enterocytes increases in enteropathic conditions including CeD, the regenerative activity in the crypts can be assessed by studying the expression of Reg1α gene and protein. [31][32][33][34] We also thought of demonstrating sequential changes in the levels of biomarkers (citrulline, I-FABP, and Reg1α) in a model where there is a cycle of normal enterocytes, predicted injury, and then recovery of enterocytes. Patients with hematological malignancy receiving high-dose chemotherapy for peripheral blood stem cell transplantation (PBSCT) could fulfil this criterion.…”

Section: Introductionmentioning

confidence: 99%

Non‐immunological biomarkers for assessment of villous abnormalities in patients with celiac disease

Singh

Verma

Das

et al. 2019

J of Gastro and Hepatol

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Background and Aim Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non‐invasive biomarker(s) that can predict the presence of villous abnormalities. Methods Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I‐FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut‐off values were derived, and the results were further validated in a prospective validation cohort. Results While level of plasma citrulline was significantly lower, the levels of plasma I‐FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten‐free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I‐FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was ≤ 30 μM/L and I‐FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut‐off values of citrulline and I‐FABP. Conclusions Plasma citrulline ≤ 30 μM/L is the most consistent, highly reproducible non‐invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.

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“…11,13,14 Das et al indicated that the rates of apoptosis in patients with mild enteropathy and advanced enteropathy were similar. 15 M30 is a caspase-cleaved keratin 18 (CK-18) cytoskeletal protein that is known to be a marker for the end of apoptosis. M65 comprises both cleaved and uncleaved CK-18 and is used as a marker for total cell death in situations of both necrosis and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…indicated that the rates of apoptosis in patients with mild enteropathy and advanced enteropathy were similar. 15 …”

Section: Introductionmentioning

confidence: 99%

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study

Aksoy¹,

Şimşek²,

Torğutalp

et al. 2018

Sao Paulo Med. J.

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BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H- scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H -score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H -score for M65 expression. There was a positive correlation between the H -score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H -score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

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Patients with mild enteropathy have apoptotic injury of enterocytes similar to that in advanced enteropathy in celiac disease

Cited by 10 publications

References 20 publications

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

Non‐immunological biomarkers for assessment of villous abnormalities in patients with celiac disease

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study

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