2011 Fiscal Year Final Research Report

Molecular immunological analysis of the pathogenesis of Wiskott Aldrich syndrome associated IgA nephropathy

Research Project

Project/Area Number	21790972
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Kanazawa University
Principal Investigator	SHIMIZU Masaki 金沢大学, 医学系, 助教 (10401902)
Project Period (FY)	2009 – 2011
Keywords	Wiskott-Aldrich症候群 / IgA腎症 / 糖鎖不全
Research Abstract	We evaluated the role of aberrant IgA production in the development of autoimmunity and glomerulonephritis in 26 patients with WAS. We found that serum galactose-deficient IgA levels and the levels of CIC containing IgA and IgG increased in WAS patients as an age dependent manner. Interestingly, these levels significantly increased in WAS patients with autoimmune manifestations. Furthermore, IgA-dominant immune deposits in the renal mesangium and glomerular injury in an XLT patient were significantly reduced after BMT. Galactose-deficient IgA levels were also markedly decreased after BMT. These findings indicate that mutations in WAS may be associated with aberrant IgA production and the development of autoimmune diseases including IgAN. Furthermore, immune reconstitution by BMT could correct aberrant IgA induced autoimmune diseases. These findings indicate that aberrant IgA production due to mutations in the WAS gene may be critically involved in the development of autoimmune diseases and glomerulonephritis.