Evidence for Increased Apoptosis of Duodenal Intraepithelial Lymphocytes in Cow's Milk Sensitive Enteropathy

Abstract

Enterocyte apoptosis induced by activated intraepithelial lymphocytes (IELs) is increased in celiac disease (CD). A lesser increment in intraepithelial lymphocytes associated with normal villous structure is also characteristic of cow's milk sensitive enteropathy (CMSE), but no information is available about the apoptosis rate of this condition. Endoscopic biopsy samples of 21 children with untreated CMSE were compared with samples from 15 children with CD and 18 controls. Apoptosis was analyzed using the TUNEL technique and the M30 antibody from duodenal bulb and mid-duodenum samples. Ki-67 was used to detect the proliferation rate and CD3(+) to count the overall number of T lymphocytes. In the mid-duodenum, CMSE patients showed a significantly increased intraepithelial and lamina propria density of TUNEL(+) cells, but no difference in the density of M30(+) epithelial cells was seen compared with controls. In CD subjects, TUNEL(+) counts in mid-duodenal villous epithelium were increased. CD3(+) intraepithelial lymphocytes were increased in both CMSE and CD and correlated with TUNEL(+) and M30(+) counts among all patients. No increase in proliferation rate was seen in CMSE, and no significant correlations between apoptosis and proliferation rates were detected. The observed increase in TUNEL(+) counts and the absence of any increase in M30(+) cells suggest that the apoptosis rate of intraepithelial lymphocytes, but not of enterocytes, is increased in the small IELs in CMSE. However, the number of intraepithelial lymphocytes is still elevated in CMSE, indicating that a disturbance of homeostasis of intraepithelial lymphocytes is important in its pathogenesis.