Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives.
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.
Sapone
Anna
A
Mucosal Biology Research Center, University of Maryland School of Medicine, 20 Penn Street, Room 345, Baltimore, MD 21201, USA.
de Magistris
Laura
L
Pietzak
Michelle
M
Clemente
Maria G
MG
Tripathi
Amit
A
Cucca
Francesco
F
Lampis
Rosanna
R
Kryszak
Deborah
D
Cartenì
Maria
M
Generoso
Maddalena
M
Iafusco
Dario
D
Prisco
Francesco
F
Laghi
Francesca
F
Riegler
Gabriele
G
Carratu
Romano
R
Counts
Debra
D
Fasano
Alessio
A
D001327:Autoimmune Diseases / Q000235:genetics / Q000503:physiopathology; D002772:Cholera Toxin / Q000235:genetics / Q000493:pharmacokinetics*; D062445:Claudin-1; D057167:Claudins; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology*; D005190:Family; D020022:Genetic Predisposition to Disease; D006242:Haptoglobins; D006801:Humans; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology*; D008565:Membrane Proteins / Q000235:genetics; D062793:Occludin; D010539:Permeability / Q000187:drug effects*; D011498:Protein Precursors
C568108:CLDN1 protein, human; C491875:CLDN2 protein, human; D062445:Claudin-1; D057167:Claudins; D006242:Haptoglobins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D011498:Protein Precursors; C408043:zonulin; D002772:Cholera Toxin