Document Detail


Genetic analysis of the influence of neuroantigen-complete Freund's adjuvant emulsion structures on the sexual dimorphism and susceptibility to experimental allergic encephalomyelitis.
MedLine Citation:
PMID:  14507669     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The induction of organ-specific autoimmune diseases, such as experimental allergic encephalomyelitis (EAE) the principal animal model of multiple sclerosis (MS), relies on the use of complete Freund's adjuvant (CFA) emulsions. In this study we report that the physical structure of the particles comprising neuroantigen-CFA emulsions significantly influences the genetic control of the incidence and sexual dimorphism seen in EAE. Immunization of (B10.S/SgMcdJ x SJL/J) F(2) mice segregating the quantitative trait loci (QTL) controlling EAE in susceptible SJL/J and resistant B10.S/SgMcdJ mice with emulsions consisting of particles where the Mycobacterium tuberculosis and neuroantigens are localized on the phase surfaces led to severe EAE in 98.8% of the mice, overriding all sex-specific and non-sex-specific genetic checkpoints. In contrast, F(2) mice immunized with emulsions where the bacterial products and encephalitogens are buried inside the water/oil vesicles exhibited a significant reduction in disease incidence (7.5%) and a sexual dimorphism (5% male versus 10% female). A genome scan identified QTL on chromosomes 7 and 11 controlling the sexual dimorphism as a function of the physical structure of the emulsion. The chromosome 11 QTL co-localizes with eae6b, and with Il12b and heptatitis A virus cellular receptor 2 (Havcr2, formerly known as Timd3), both of which are candidate genes for this QTL. Sequence analysis of the SJL/J and B10.S/SgMcdJ alleles indicates that both gene products are structurally monomorphic. Expression analysis also excluded both as candidates for this sex-specific QTL. These results reinforce the importance of gene-environment interactions in initiating and propagating autoimmune disease of the central nervous system, particularly in the context of susceptibility to MS and disease heterogeneity.
Authors:
Parley D Fillmore; Matthew Brace; Scott A Troutman; Elizabeth P Blankenhorn; Sean Diehl; Mercedes Rincon; Cory Teuscher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  163     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-09-25     Completed Date:  2003-10-29     Revised Date:  2013-06-09    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1623-32     Citation Subset:  AIM; IM    
Affiliation:
Department of Veterinary Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence / genetics
Animals
Antigens, Bacterial / immunology*
Central Nervous System / immunology*
Chromosome Mapping
DNA, Complementary / genetics
Drug Combinations
Emulsions
Encephalomyelitis, Autoimmune, Experimental / genetics*,  immunology*
Female
Freund's Adjuvant / immunology*
Genetic Linkage
Genetic Predisposition to Disease
Genome
Male
Mice
Mice, Inbred Strains
Molecular Sequence Data
Mycobacterium tuberculosis / immunology*
Quantitative Trait Loci
Receptors, Virus / genetics
Sex Characteristics
Grant Support
ID/Acronym/Agency:
AI41747/AI/NIAID NIH HHS; AI45105/AI/NIAID NIH HHS; NS255195/NS/NINDS NIH HHS; NS36526/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Bacterial; 0/DNA, Complementary; 0/Drug Combinations; 0/Emulsions; 0/Havcr2 protein, mouse; 0/Receptors, Virus; 9007-81-2/Freund's Adjuvant
Comments/Corrections

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