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

Scand J Gastroenterol. 2005 Dec;40(12):1398-406. doi: 10.1080/00365520510023765.


Objective: Pathogenetic mechanisms of cow's milk protein-sensitive enteropathy (CMSE) are poorly defined, but elevated serum granzyme levels and an increase in duodenal intraepithelial lymphocytes (IELs) expressing TIA-1 suggest the involvement of abnormal lymphocyte cytotoxicity. To evaluate cytotoxicity in CMSE we analysed the expression of cytotoxic granule components in duodenal IELs. For comparison, we studied subjects with coeliac disease (CD), in which lymphocyte cytotoxicity is pathogenically important.

Material and methods: Fifty-four children were examined by endoscopy for gastrointestinal complaints. Twenty-one subjects had a final diagnosis of CMSE, 15 children had untreated CD and 18 controls showed no definite gastrointestinal disease. Mucosal samples furnished from the bulb and descending duodenum were stained for CD3, perforin, granzymes A and B and TIA-1.

Results: In both CMSE and CD, increase of mid-duodenal TIA-1, perforin and granzyme A expressing IELs was seen, the counts in CD being much higher, and increased expression was also seen in the bulb. Granzyme B expression was increased only in CD. In CMSE, no evidence of villous atrophy was seen.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Celiac Disease / metabolism*
  • Celiac Disease / pathology
  • Child
  • Child, Preschool
  • Duodenum / metabolism
  • Duodenum / pathology
  • Female
  • Gastrointestinal Diseases / metabolism*
  • Gastrointestinal Diseases / pathology
  • Granzymes
  • Humans
  • Male
  • Membrane Glycoproteins / metabolism*
  • Milk Hypersensitivity / metabolism*
  • Milk Hypersensitivity / pathology
  • Milk Proteins / adverse effects
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • RNA-Binding Proteins / metabolism*
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / physiology


  • Membrane Glycoproteins
  • Milk Proteins
  • Pore Forming Cytotoxic Proteins
  • RNA-Binding Proteins
  • Perforin
  • TIAL1 protein, human
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases
  • GZMA protein, human