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THE EFFECT OF A GLUTEN-FREE DIET AND GENETIC FACTORS ON APOPTOTIC ACTIVITY OF THE SMALL INTESTINE IN CHILDREN WITH CELIAC DISEASE | ||||
Jernej Dolinšek Department of Paediatrics, University Medical Centre Maribor, Slovenia |
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Background: Celiac disease is an immunologically mediated disease of the small intestine induced by gluten ingestion in genetically predisposed individuals. The diagnosis of the disease is based on the assessment of a specific antibody pattern and histological changes of the intestinal mucosa, better known as villous atrophy. The precise mechanisms of mucosal damage have not been definitively explained, but it is believed to be caused by a complex aberrant immune response to gluten in genetically predisposed individuals. Aim: The aim of our study was to determine whether enterocyte apoptosis is increased in children with active celiac disease compared to patients on a gluten-free diet. In addition, we sought to determine which predisposing genes are found in our celiac patients, and the correlation between enterocyte apoptosis and specific histological changes of the intestinal mucosa, especially the count of IEL carrying gamma/delta T-cell receptor (gamma/delta IEL). Methods: 15 children
with active celiac disease, aged 5.8±4.1 years, 15 celiac patients on a
gluten-free diet, aged 8.9±4.3 years, and 15 controls, aged 7.9±5.1 years,
were included in the study. The presence of HLA-DQ2 or HLA-DQ8 was
determined in all patients. Intestinal biopsy was performed and histological
changes were determined using the Marsh classification, based on the
intraepithelial lymphocyte (IEL) count, crypt hyperplasia and villous
atrophy. Immunohistochemical methods were used to assess the total IEL count,
and the counts of alpha/beta IEL and gamma/delta IEL. The apoptotic index
was calculated using the TUNEL (terminal uridine deoxynucleotide nick end
labeling) method. Results: All children
with celiac disease included in our study carry the common predisposing
genes for HLA-DQ2 (90%) or HLA-DQ8 (10%), whereas in the control group other
genes were more common. The degree of villous atrophy differed significantly
between groups. Children with active celiac disease showed a higher
frequency of severe mucosal lesions (20% type 2 and 80% type 3), than
patients on a gluten-free diet. Conclusion: Mucosal changes typical of celiac disease are related to increased enterocyte apoptosis in children. IEL could play an important role in this process, since their numbers are significantly increased both in children with active celiac disease and patients on a gluten-free diet. Activation of these lymphocytes by gluten could be an inducing factor for enterocyte apoptosis, which eventually leads to villous atrophy. Continuous activation of IEL could also be responsible for their malignant alteration and development of malignant lymphoma in patients with untreated celiac disease. Key words: celiac disease, children, apoptosis, intraepithelial lymphocytes, genetics, histology. |