Level of galactosylation determines cryoglobulin activity of murine IgG3 monoclonal rheumatoid factor.

Blood
Aki KurokiS Izui

Abstract

Autoantibodies of the cryoprecipitating IgG3 isotype have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. At present, the structural basis of IgG3 cryoprecipitation and its role in autoantibody pathogenicity remain to be defined. Using molecular variants of an IgG3 monoclonal rheumatoid factor, 6-19, derived from an autoimmune MRL-Fas(lpr) mouse, we have investigated the implication of charged residues in the heavy-chain variable (VH) region, potential CH3-linked oligosaccharides, and galactosylation of CH2-linked oligosaccharides in its cryoglobulin activity. The cryoglobulin activity of the IgG3 6-19 mutant bearing more negatively charged residues at VH 6 and 23 was found to be reduced but still highly significant, whereas that of the mutant lacking a potential CH3 glycosylation site remained unchanged. In marked contrast, IgG3 6-19 variants obtained from 6-19 heavy-chain transgenic mice displayed barely detectable cryoglobulin activity associated with an increased level of galactosylation in the CH2 oligosaccharide side chains. Thus, our data strongly suggest that the cryoglobulin activity of IgG3 6-19 autoantibody is critically determined by levels of galactosylation in the...Continue Reading

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Citations

Sep 6, 2006·Springer Seminars in Immunopathology·Lucie BaudinoShozo Izui
Jun 9, 2006·Bulletin of Experimental Biology and Medicine·N A Konstantinova, E N Karandashov
Apr 7, 2007·Bulletin of Experimental Biology and Medicine·E N KarandashovA N Komarov
Oct 22, 2013·La Revue de médecine interne·R GoulabchandP Guilpain
Apr 15, 2008·Current Opinion in Nephrology and Hypertension·Charles E Alpers, Kelly D Smith
Oct 2, 2012·Journal of the American Society of Nephrology : JASN·Masako OtaniShozo Izui
May 11, 2010·Journal of Periodontology·Gavrilo BrajovićNadezda Milosević-Jovcić
Jan 6, 2006·Kidney International·S H NasrV D D'Agati
Sep 28, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Jonathan Maurice ChemounyRenato C Monteiro
Mar 25, 2014·Autoimmunity Reviews·Radjiv GoulabchandPhilippe Guilpain
Jul 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasuhiro KurodaShozo Izui
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucie BaudinoShozo Izui
Oct 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucie BaudinoShozo Izui
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