Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease

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

doi:10.1016/j.jaci.2004.10.009

Cited by 17 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We did not investigate whether elimination of milk proteins from the diet would normalize the expression of cytotoxicity-related proteins. However, the results of our previous studies indicate that this abnormality is associated with the use of milk antigens [23,24]. Our findings help us to understand the pathogenesis of CMSE and have implications in the diagnostic assessment of a suspected disease.…”

Section: Discussionmentioning

confidence: 64%

“…We have recently found elevated levels of serum granzymes A and B in CMSE, indicating occurrence of cell-mediated cytoxicity [23]. In addition, we have observed increased TIA-1 expression in IELs in preschool and school-age children with CMSE [24], further suggesting an increase of lymphocyte cytotoxicity in this condition, while in lamina propria lymphocytes, no increase of TIA-1 expression was seen [24].…”

Section: Introductionmentioning

confidence: 68%

“…We have recently shown that serum granzyme concentrations in CMSE are even higher than those in CD [23]. Since serum granzymes probable originate from cytotoxic lymphocytes in the intestinal mucosa in both CMSE and CD [23], it is likely that mucosal cytotoxic granule proteins expressing lymphocytes are truly activated even in CMSE.…”

Section: Discussionmentioning

confidence: 99%

“…Since serum granzymes probable originate from cytotoxic lymphocytes in the intestinal mucosa in both CMSE and CD [23], it is likely that mucosal cytotoxic granule proteins expressing lymphocytes are truly activated even in CMSE. In our previous analysis, we did not find any evidence of increased enterocyte apoptosis or compensatory proliferation, but there was some indirect evidence for increased rate of apoptosis of IELs [25].…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

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

Augustin

Kokkonen

Karttunen

2005

Scandinavian Journal of Gastroenterology

Self Cite

View full text Add to dashboard Cite

Increase in duodenal IELs expressing cytotoxic granules is a characteristic feature in CMSE, although to a lesser degree than in CD. Cytotoxicity is suggested to be involved in the pathogenesis of intestinal dysfunction in CMSE, but based on the absence of villous abnormalities may not be mainly targeted to enterocytes. The mechanisms leading to the accumulation of these cells in CMSE need further investigation.

show abstract

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

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

Augustin

Kokkonen

Karttunen

2005

Scandinavian Journal of Gastroenterology

Self Cite

View full text Add to dashboard Cite

show abstract

“…All CD subjects were positive for endomysium antibodies. The same series of patients had been used in previous studies evaluating granzymes (4), mucosal apoptosis (15), cytotoxic lymphocytes (2), gamma/delta T-cell receptor expression (16) and cytokine profiles (17). For the Western blot analysis we had an additional series of3 patients with untreated CD (mean age 6.3 years, range 4-11 years; 2 females) and 4 control subjects (mean age 8.2 years, range 6-10 years, 1 female).…”

Section: Patientsmentioning

confidence: 99%

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

Food Protein‐Induced Enterocolitis and Enteropathies

Lieberman

Nowak‐Węgrzyn

2013

Food Allergy

View full text Add to dashboard Cite

Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease

Cited by 17 publications

References 30 publications

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

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

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

Food Protein‐Induced Enterocolitis and Enteropathies

Contact Info

Product

Resources

About