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ENTEROCYTIC CYP3A4 IN ADULT POPULATION: CORRELATION WITH HEMOGLOBIN AND ANTI TTG LEVEL IN CELIAC DISEASE
N Khalifa, G Dresser, D Driman, J Parfitt University of Western Ontario, London, Ontario
AIMS: We previously demonstrated in pediatric patients with celiac disease that there was a correlation between CYP3A4 staining intensity in the duodenum and the Hb blood level and TTG but there was no association between the disease pathology as per March classification and CYP3A4 staining. Hence, we wanted to know whether such findings exist in adults.
The aims of this study is to investigate the effect of celiac disease severity as expressed by Hb and anti TTG level, on the amount of CYP3A4 in the duodenal mucosa as expressed by its staining under light microscope and to evaluate the usefulness of March classification in defining the disease severity.
METHODS: Duodenal biopsies were collected from 48 adult patients (age range 18 to 37 years). 22 patients were excluded because of lack of pathologic evidence of celiac disease (11 patients) or lack of TTG level abnormality at any point (5 patients) or because Hb level was unknown (6 patients). Among the remaining 26 patients, CYP3A4 concentration was assessed by immunohistochemistry staining using the mean of a subjective scoring (from 0 to 4) based on the intensity of the stain under light microscope. The score was compared to the degree of Hb and TTG level to see if any correlation exists. March classification (A to D) was also compared to the score of the CYP3A4 staining to decide if any association exists.
RESULTS: In the 26 duodenal biopsies of celiac disease patients, the intensity of CYP3A4 staining was found to be inversely related to the TTG level whence it exceeds the value of 10 or more. No clear correlation exists between Hb and CYP3A4 staining intensity whence Hb level is above 130. As the disease gets advanced (as evidenced by March classification), the CYP3A4 amount in the duodenum drops.
CONCLUSIONS: Duodenal CYP3A4 is present at significantly lower levels in patients with higher TTG levels. This may have clinical significance with respect to the oral bioavailability of CYP3A4 substrates. March classification is a useful tool in assessing disease severity in adult patients as compared to pediatric patients with celiac disease.