Duodenal cytotoxic lymphocytes in cow's milk protein sensitive enteropathy and coeliac disease

Augustin, Merja T.; Kokkonen, Jorma; Karttunen, Tuomo J.

doi:10.1080/00365520510023765

Cited by 20 publications

(18 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with untreated food allergy express equal densities of total intraepithelial CD3+ and alpha/beta + T-cells but significantly higher densities of gamma/delta + cells and gamma/delta + /CD3+ ratio than patients currently on an elimination diet for food allergy or healthy controls [88][89][90].…”

Section: Non-celiac Gluten Sensitivitymentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: Literature Review

Mansueto

Seidita

D’Alcamo

et al. 2014

Journal of the American College of Nutrition

View full text Add to dashboard Cite

Key words: non-celiac gluten sensitivity, celiac disease, wheat allergy, food allergy, HLA, flow cytometric basophil activation test, innate immune response Background: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS).Aim: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients.Methods: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS.Results: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.Conclusions: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points:• Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet.• NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy.• Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course.• A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.• Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup. Abbreviations: CD = celiac disease, WA = wheat allergy, NCGS = non-celiac gluten sensitivity, GFD = gluten-free diet, IBS = irritable bowel syndrome, HLA = human leukocyte antigen, tTg = antitissue transglutaminase, AGA = antigliadin antibodies, EMA = endomysial antigen, DGP = deami...

show abstract

Section: Non-celiac Gluten Sensitivitymentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: Literature Review

Mansueto

Seidita

D’Alcamo

et al. 2014

Journal of the American College of Nutrition

View full text Add to dashboard Cite

show abstract

“…From 5% to 15% of CD3 þ IELs are TCRgd þ , and the remaining cells, CD3 -and without specific markers of lymphoid T and B lineages, include precursors of CD3 þ T cells and other lymphocytes resembling peripheral blood NK cells (PB-NKs) (8,9). Changes in IEL features or distribution of the subsets have been observed in viral and parasitic entheropathies (10), HIV infection (11,12), cow's milk protein sensitivity (13,14), or intestinal bowel disease (15,16). Some authors support the diagnostic usefulness of IEL phenotyping in celiac disease and its complications, based on the finding of a specific pattern consisting of increased IEL infiltration, high levels of TCRgd þ , and low levels of CD3 -cells (17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts

Talayero

Mancebo

Pulido

et al. 2016

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Previous reports demonstrate the role of PI-9 in the protection of cells against misdirected GrB during immune activation in endothelium and mesothelium (9). This might also be the case in duodenal epithelium as the enterocytes ofduodenum are continuously in the vicinity of GrB expressing IELs which function to protect the epithelium from pathogens (2). PI-9 expression was also seen in various lamina propria cells including lymphocytes in both control and CD patients.…”

Section: Discussionmentioning

confidence: 72%

“…After a 10-min washing procedure, visualization was performed using EnVision solution for 30 min and the sections were washed in PBS-Tween for 15 min with three changes. The stainings for OrB, terminal deoxynucleotidyl transferase-mediated digoxigenindeoxyuridine triphosphate nick end labeling (TUNEL) and CD3+, a1~+, and y/8+ lymphocytes were performed as previously described (2,4,15).…”

Section: Patientsmentioning

confidence: 99%

“…GrB is a key effector in the apoptosis-inducing granule pathway (3). Elevated GrB serum levels and increased expression of GrB in IELs in the small intestine have been documented in CD (2,4). The only known endogenous GrB inhibitor is a serine protease inhibitor called protease inhibitor 9 (PI-9), which has been documented to efficiently inhibit GrB-mediated apoptosis (3,5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Decreased Expression of Protease Inhibitor 9, a Granzyme B Inhibitor, in Celiac Disease: A Potential Mechanism in Enterocyte Destruction and Villous Atrophy

Pohjanen

Arvonen

et al. 2013

Int J Immunopathol Pharmacol

View full text Add to dashboard Cite

The objective of this study was to assess the expression of protease inhibitor 9, a granzyme B inhibitor, in human small intestine, and to evaluate its cytoprotective role in the celiac disease of children. Twelve subjects with untreated celiac disease and thirteen healthy controls were examined by endoscopy. The expression of protease inhibitor 9 was analyzed immunohistochemically from duodenal biopsies and compared to granzyme B expression, apoptosis rate, number of intraepitheliallymphocytes and villus and crypt height data from the biopsies. We discovered that protease inhibitor 9 is expressed in the cytoplasm of the duodenal epithelial cells in the majority of cases. The enterocyte expression of protease inhibitor 9 was lower in celiac disease patients than in controls. Protease inhibitor 9 expression also showed a negative correlation with the number of apoptotic cells, overall density of granzyme B expressing intraepithelial lymphocytes, the height of the crypts and the severity of villous atrophy in duodenum. Therefore, we conclude that the protease inhibitor 9 is constantly expressed in the enterocytes of normal duodenum and the expression is decreased in celiac disease. These findings suggest that protease inhibitor 9 has a role in duodenal homeostasis and in the protection of enterocytes from misdirected granzyme B. Indeed, observed associations of lowered protease inhibitor 9 expression together with increased granzyme B expression, apoptosis rate and severity of villous atrophy suggest that impaired balance between granzyme B mediated cytotoxicity and its inhibition by protease inhibitor 9 forms an important factor in the pathogenesis of villous atrophy in celiac disease.

show abstract

Duodenal cytotoxic lymphocytes in cow's milk protein sensitive enteropathy and coeliac disease

Cited by 20 publications

References 34 publications

Non-Celiac Gluten Sensitivity: Literature Review

Non-Celiac Gluten Sensitivity: Literature Review

Innate Lymphoid Cells Groups 1 and 3 in the Epithelial Compartment of Functional Human Intestinal Allografts

Decreased Expression of Protease Inhibitor 9, a Granzyme B Inhibitor, in Celiac Disease: A Potential Mechanism in Enterocyte Destruction and Villous Atrophy

Contact Info

Product

Resources

About