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O-glycosylated IgA rheumatoid factor induces IgA deposits and glomerulonephritis

Wada, Yoshinao
Published in Journal of the American Society of Nephrology. 2012, vol. 23, no. 3, p. 438-46
Abstract Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA- and 46-42 IgA-injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor-induced GN could serve as an experimental model for IgA nephropathy.
Keywords Amino Acid SequenceAnimalsAntibodies, Monoclonal/adverse effects/analysisComplement C3/metabolismDisease Models, AnimalGlomerulonephritis/etiology/metabolism/pathologyGlomerulonephritis, IGA/etiology/metabolism/pathologyHybridomas/metabolismImmunoglobulin A/immunology/metabolismImmunoglobulin Allotypes/metabolismImmunoglobulin G/immunology/metabolismMiceMice, Inbred BALB CMolecular Sequence DataRheumatoid Factor/metabolism
PMID: 22193386
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Research group Analyse protéomique et Analyse génomique des maladies rénales (659)
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OTANI, Masako et al. O-glycosylated IgA rheumatoid factor induces IgA deposits and glomerulonephritis. In: Journal of the American Society of Nephrology, 2012, vol. 23, n° 3, p. 438-46. doi: 10.1681/ASN.2011070701 https://archive-ouverte.unige.ch/unige:43826

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Deposited on : 2014-12-18

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