The caffeine metabolic ratio as an index of xanthine oxidase activity in clinically active and silent celiac patients

Background: The xanthine oxidoreductase system has been identified as one of the main sources of free radicals responsible for various forms of tissue injury. Because the intestinal villi are an important location of this enzyme, it was of interest to study the role of xanthine oxidase in gluten-sensitive celiac enteropathy, associated with characteristic villous atrophy. Measured by a noninvasive method, the ratio of caffeine metabolites excreted in the urine after a caffeine challenge had previously been shown to be indicative of the total xanthine oxidase activity of the patient. Methods: The study involved 22 children with gluten-challenged celiac disease, exhibiting subtotal villous atrophy in specimens from the third intestinal biopsy in accordance with ESPGHAN criteria. Ten of the patients displayed overt clinical symptoms (active form), whereas 12 had no symptoms (silent form). Urinary caffeine metabolites were determined by high-pressure liquid chromatography. The total in vivo xanthine oxidase activity was expressed as the caffeine metabolite index. Results: In patients with active celiac disease the xanthine oxidase activity index was considerably higher, whereas in those with silent disease it was significantly lower than the control value. A significant negative correlation was shown between the index indicative of xanthine oxidase activity and the serum iron level of the patients. Conclusions: Activation of xanthine oxidase may play a role in the pathogenesis of active celiac disease with definite malabsorption, gastrointestinal symptoms, and anemia. The caffeine test reflects the difference in the pathogenetic mechanism leading to the mucosal lesion and clinical symptoms of active and silent forms of celiac disease.