Sapone, Anna, de Magistris, Laura, Pietzak, Michelle, Clemente, Maria G., Tripathi, Amit, Cucca, Francesco, Lampis, Rosanna, Kryszak, Deborah, Cartenì, Maria, Generoso, Maddalena, Iafusco, Dario, Prisco, Francesco, Laghi, Francesca, Riegler, Gabriele, Carratu, Romano, Counts, Debra, and Fasano, Alessio
Zonulin, a protein that modulates intestinal permeability, is upregulated in several autoimmune diseases and is involved in the pathogenesis of autoimmune diabetes in the BB/Wor animal model of the disease. To verify the association between serum zonulin levels and in vivo intestinal permeability in patients with type 1 diabetes, both parameters were investigated in different stages of the autoimmune process. Forty-two percent (141 of 339) of the patients had abnormal serum zonulin levels, as compared with age-matched control subjects. The increased zonulin levels correlated with increased intestinal permeability in vivo and changes in claudin-1, claudin-2, and myosin IXB genes expression, while no changes were detected in ZO1 and occludin genes expression. When tested in serum samples collected during the pre-type 1 diabetes phase, elevated serum zonulin was detected in 70% of subjects and preceded by 3.5 ± 0.9 years the onset of the disease in those patients who went on to develop type 1 diabetes. Combined, these results suggest that zonulin upregulation is associated with increased intestinal permeability in a subgroup of type 1 diabetic patients. Zonulin upregulation seems to precede the onset of the disease, providing a possible link between increased intestinal permeability, environmental exposure to non-self antigens, and the development of autoimmunity in genetically susceptible individuals. Diabetes 55:1443-1449, 2006 [ABSTRACT FROM AUTHOR]