Document Detail


A critical role for sialylation in cryoglobulin activity of murine IgG3 monoclonal antibodies.
MedLine Citation:
PMID:  16002706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cryoprecipitating IgG3 autoantibodies have been shown to play a significant role in the development of murine lupus-like autoimmune syndrome. However, the structural basis of IgG3 cryoprecipitation still remains to be defined. In view of the implication of positively charged amino acid residues present in variable regions in IgG3 cryoglobulin activity, we explored the role of terminal sialic acids in oligosaccharide side chains for the cryogenic activity of IgG3 mAb. Comparative oligosaccharide structural analysis of different cryogenic and non-cryogenic IgG3 mAb showed an inverse correlation between the extent of sialylation and cryogenic activity. The inhibitory role of sialylation was further confirmed by the demonstration of enrichment of less and more sialylated IgG3 in cryoprecipitated and noncryoprecipitated fractions, respectively, separated from four different cryogenic IgG3 mAb. Significantly, the sialic acid contents of the latter fraction became comparable to those of non-cryogenic IgG3 mAb. Finally, we observed that highly sialylated non-cryogenic IgG3 mAb was more potent in the inhibition of cryoprecipitation of cryogenic IgG3 mAb. Our results thus suggest that the content of negatively charged sialic acids in oligosaccharide side chains is one of the critical factors to determine IgG3 cryoglobulin activity, along with amino acid sequences of the IgG3 variable regions.
Authors:
Yasuhiro Kuroda; Aki Kuroki; Shuichi Kikuchi; Takaaki Funase; Munehiro Nakata; Shozo Izui
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-08     Completed Date:  2005-09-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1056-61     Citation Subset:  AIM; IM    
Affiliation:
Institute of Glycotechnology and Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / chemistry,  genetics,  metabolism*
Carbohydrate Sequence
Centrifugation
Chemical Precipitation
Cryoglobulins / antagonists & inhibitors,  isolation & purification,  metabolism*
Freezing
Galactose / chemistry,  metabolism
Humans
Immunoglobulin G / chemistry,  genetics,  isolation & purification,  metabolism*
Mice
Mice, Inbred MRL lpr
Mice, Transgenic
Molecular Sequence Data
Oligosaccharides / chemistry,  isolation & purification,  metabolism
Sialic Acids / chemistry*,  metabolism*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Cryoglobulins; 0/Immunoglobulin G; 0/Oligosaccharides; 0/Sialic Acids; 26566-61-0/Galactose

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