Increased small intestinal apoptosis in coeliac disease

Area of Science:

• Gastroenterology
• Immunology
• Cell Biology

Background:

• Coeliac disease (CD) is characterized by flattened mucosa despite increased epithelial cell proliferation.
• The mechanisms driving cell loss in CD remain incompletely understood.

Purpose of the Study:

• To investigate the mechanisms of enterocyte cell loss in coeliac disease.
• To quantify programmed cell death (apoptosis) in the small intestinal mucosa of CD patients.

Main Methods:

• Small intestinal biopsy specimens from controls, active CD patients, and patients on a gluten-free diet were analyzed.
• Terminal uridine deoxynucleotidyl nick end labelling (TUNEL) was used to detect apoptotic cells.
• Immunostaining for Ki-67 identified proliferating cells, and CD45 antibodies traced the origin of apoptotic cells.

Main Results:

• Apoptosis was significantly increased in active CD patients compared to controls, distributed throughout the crypt-villus unit.
• The number of apoptotic cells correlated positively with the number of proliferating cells (Ki-67 positive cells).
• Enterocyte apoptosis decreased to normal levels in CD patients following a gluten-free diet, even before complete histological normalization.

Conclusions:

• Enterocyte apoptosis is markedly elevated in untreated coeliac disease and is a significant contributor to villous atrophy.
• The increased apoptosis in CD is directly related to epithelial cell proliferation.
• A gluten-free diet effectively reduces enterocyte apoptosis to normal levels, independent of immediate histological improvement.