title: Development of IgA nephropathy-like glomerulonephritis associated with Wiskott-Aldrich syndrome protein deficiency.
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.
authors.affiliation: Disorders of Immunity Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.forename: N P
authors.initials: NP
authors.lastname: Nikolov
authors.forename: K
authors.initials: K
authors.lastname: Ueno
authors.forename: K
authors.initials: K
authors.lastname: Ohta
authors.forename: R M
authors.initials: RM
authors.lastname: Siegel
authors.forename: A
authors.initials: A
authors.lastname: Yachie
authors.forename: F
authors.initials: F
authors.lastname: Candotti
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D013921:Thrombocytopenia / Q000378:metabolism; D014923:Wiskott-Aldrich Syndrome / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000172:deficiency*
chemical_list: D007070:Immunoglobulin A; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein
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