Chimeric Human Anti-Gliadin Monoclonal antibody, clone 9E23

Dietary gliadin may show a broad spectrum of toxicity. The interplay between mitochondria and gliadin-induced oxidative stress has not been thoroughly examined in the intestinal epithelium. In this kinetic study, Caco-2 cells were exposed for 24 h to pepsin-trypsin-digested gliadin, alone or in combination with the antioxidant 2,6-di-tbutyl-p-cresol (BHT), and the effects on mitochondrial biogenesis and mtDNA were studied. Cells ability to recover from stress was determined after 24 h and 48 h of incubation in the culture medium. Gliadin-induced oxidative stress evoked a compensatory response. The stressor triggered a rapid and significant increase of Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1) and Peroxiredoxin III (PrxIII) proteins, and mtDNA amount. As for the effects of gliadin on mtDNA integrity, strand breaks, abasic sites, and modified bases were analyzed in three mtDNA regions. D-loop appeared a more fragile target than Ori-L and ND1/ND2. The temporal trend of the damage at D-loop paralleled that of the amount of mtDNA. Overall, a trend toward control values was shown 48 h after gliadin exposure. Finally, BHT was able to counteract the effects of gliadin. Results from this study highlighted the effects of gliadin-induced oxidative stress on mitochondria, providing valuable evidence that might improve the knowledge of the pathophysiology of gluten-related disorders.

Celiac disease is an immune-mediated systemic disorder with enteropathy, which is triggered by the grain protein gluten in genetically predisposed individuals. Untreated it can lead to nutrient deficiencies, impaired growth, osteoporosis, and other long-term complications. The prevalence in Germany is relatively high (ca. 1.0%) and can reach up to 15% in risk groups. While the classical gastrointestinal manifestations with chronic diarrhea, malabsorption syndrome and failure to thrive only occur in a minority of affected patients, most children and adults with celiac disease show no or only unspecific symptoms, such as constipation or extraintestinal signs, e.g. iron deficiency anemia and elevated liver enzymes. If celiac specific antibodies are positive the patient should be referred to a pediatric gastroenterologist for further confirmation of the diagnosis. The only available but extremely effective treatment is still a life-long strict gluten-free diet.