1. Development of IgA nephropathy-like glomerulonephritis associated with Wiskott–Aldrich syndrome protein deficiency
- Author
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Masaki Shimizu, Fabio Candotti, Akihiro Yachie, Kazuyuki Ueno, Nikolay P. Nikolov, Kazuhide Ohta, and Richard M. Siegel
- Subjects
Immunoglobulin A ,Glycosylation ,Wiskott–Aldrich syndrome ,Immunology ,Spleen ,macromolecular substances ,Article ,Nephropathy ,Pathogenesis ,Mice ,Immune system ,medicine ,Animals ,Humans ,Immunology and Allergy ,Mice, Knockout ,B-Lymphocytes ,biology ,business.industry ,Glomerulonephritis, IGA ,Glomerulonephritis ,medicine.disease ,Thrombocytopenia ,Wiskott-Aldrich Syndrome ,Disease Models, Animal ,medicine.anatomical_structure ,biology.protein ,business ,Complication ,Wiskott-Aldrich Syndrome Protein - Abstract
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder caused by mutations in the WAS gene. Glomerulonephritis is a frequent complication, however, histopathological data from affected patients is scarce because the thrombocytopenia that affects most patients is a contraindication to renal biopsies. We found that WASp-deficient mice develop proliferative glomerulonephritis reminiscent of human IgA nephropathy (IgAN). We examined whether increased aberrant IgA production is associated with the development of glomerulonephritis in WASp-deficient mice. Serum IgA and IgA production by splenic B cells was increased in WASp-deficient mice compared to wild-type (WT) mice. A lectin-binding study revealed a reduced ratio of sialylated and galactosylated IgA in the sera from old WASp-deficient mice. Circulating IgA-containing immune complexes showed significantly higher titers in WASp-deficient mice compared to WT mice. These results indicate that the increased IgA production and aberrant glycosylation of IgA may be critically involved in the pathogenesis of glomerulonephritis in WAS.
- Published
- 2012