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Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction.
- Source :
-
Kidney international [Kidney Int] 2015 Aug; Vol. 88 (2), pp. 276-85. Date of Electronic Publication: 2015 Mar 25. - Publication Year :
- 2015
-
Abstract
- IgA1 complexes containing deglycosylated IgA1, IgG autoantibodies, and a soluble form of the IgA receptor (sCD89), are hallmarks of IgA nephropathy (IgAN). Food antigens, notably gluten, are associated with increased mucosal response and IgAN onset, but their implication in the pathology remains unknown. Here, an IgAN mouse model expressing human IgA1 and CD89 was used to examine the role of gluten in IgAN. Mice were given a gluten-free diet for three generations to produce gluten sensitivity, and then challenged for 30 days with a gluten diet. A gluten-free diet resulted in a decrease of mesangial IgA1 deposits, transferrin 1 receptor, and transglutaminase 2 expression, as well as hematuria. Mice on a gluten-free diet lacked IgA1-sCD89 complexes in serum and kidney eluates. Disease severity depended on gluten and CD89, as shown by reappearance of IgAN features in mice on a gluten diet and by direct binding of the gluten-subcomponent gliadin to sCD89. A gluten diet exacerbated intestinal IgA1 secretion, inflammation, and villous atrophy, and increased serum IgA1 anti-gliadin antibodies, which correlated with proteinuria in mice and patients. Moreover, early treatment of humanized mice with a gluten-free diet prevented mesangial IgA1 deposits and hematuria. Thus, gliadin-CD89 interaction may aggravate IgAN development through induction of IgA1-sCD89 complex formation and a mucosal immune response. Hence, early-stage treatment with a gluten-free diet could be beneficial to prevent disease.
- Subjects :
- Animals
Antigens, CD blood
Atrophy etiology
Diet, Gluten-Free
Disease Models, Animal
Enteritis etiology
GTP-Binding Proteins metabolism
Gliadin immunology
Gliadin metabolism
Glomerulonephritis, IGA diet therapy
Glutens administration & dosage
Glutens immunology
Hematuria diet therapy
Hematuria etiology
Immunoglobulin A blood
Intestinal Mucosa immunology
Intestinal Mucosa metabolism
Male
Mice
Protein Glutamine gamma Glutamyltransferase 2
Proteinuria etiology
Receptors, Fc blood
Receptors, Transferrin metabolism
Transglutaminases metabolism
Antigens, CD metabolism
Glomerulonephritis, IGA immunology
Glomerulonephritis, IGA metabolism
Glutens toxicity
Immunoglobulin A metabolism
Intestinal Mucosa pathology
Receptors, Fc metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 88
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 25807036
- Full Text :
- https://doi.org/10.1038/ki.2015.94