Document Detail

Molecular mimicry between insulin and retroviral antigen p73. Development of cross-reactive autoantibodies in sera of NOD and C57BL/KsJ db/db mice.
MedLine Citation:
PMID:  3286334     Owner:  NLM     Status:  MEDLINE    
Enzyme-linked immunosorbent assay (ELISA) was used to study temporal development of murine autoantibodies against insulin and both type C and intracisternal type A retroviral antigens. The nonobese diabetic (NOD) mouse, a model for autoimmune, insulin-dependent diabetes, was compared with a related, but diabetes-resistant, strain, nonobese normal (NON). Similarly, C57BL/KsJ db/db mice (insulin-resistant model of insulin-dependent diabetes and obesity) were compared with diabetes-resistant C57BL/6 db/db mice. NOD mice developed much higher autoantibody titers than did NON mice. Whereas type C autoantibodies in NOD developed to peak titer shortly after mice were weaned, autoantibodies against insulin and p73 (group-specific antigen of the intracisternal type A particle) did not develop until shortly before, or concomitant with, the development of hyperglycemia. Two NOD mice not developing hyperglycemia during the 40-wk study period were distinguished from the mice developing diabetes by a delayed onset of insulin (but not p73) autoantibodies. Our findings suggest that in NOD mice, the appearance of insulin and p73 autoantibodies signifies that extensive underlying necrosis of beta-cells occurred. C57BL/KsJ db/db mice (with extensive beta-cell necrosis and early hyperglycemia) developed much higher autoantibody titers to insulin and p73 than did the diabetes-resistant C57BL/6 db/db mice. However, the presence of autoantibodies in normoglycemic C57BL/KsJ +/db controls demonstrated that elevated autoantibody titers alone were insufficient to produce diabetes in this model. Absorption studies indicated that autoantibodies against p73 recognized a common epitope on insulin and IgE-binding factor. The potential significance of this molecular mimicry is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
D V Serreze; E H Leiter; E L Kuff; P Jardieu; K Ishizaka
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  37     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  1988 Mar 
Date Detail:
Created Date:  1988-07-14     Completed Date:  1988-07-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  351-8     Citation Subset:  AIM; IM    
Jackson Laboratory, Bar Harbor, ME 04609.
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MeSH Terms
Antibody Formation
Antigens, Viral / immunology*
Autoantibodies / analysis*
Cross Reactions
Diabetes Mellitus, Experimental / immunology*
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Gene Products, gag
Immunoglobulin G / analysis
Immunoglobulin M / analysis
Insulin / immunology*
Lymphokines / immunology
Mice, Inbred C57BL
Mice, Mutant Strains
Prostatic Secretory Proteins*
Retroviridae Proteins / immunology*
Reg. No./Substance:
0/Antigens, Viral; 0/Autoantibodies; 0/Gene Products, gag; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Lymphokines; 0/Prostatic Secretory Proteins; 0/Retroviridae Proteins; 0/beta-microseminoprotein; 0/immunoglobulin-binding factors; 11061-68-0/Insulin

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