Document Detail


Maternal MHC regulates generation of pathogenic antibodies and fetal MHC-encoded genes determine susceptibility in congenital heart block.
MedLine Citation:
PMID:  20696861     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Congenital heart block develops in fetuses of anti-Ro52 Ab-positive women. A recurrence rate of 20%, despite the persistence of maternal autoantibodies, indicates that there are additional, yet unidentified, factors critical for development of congenital heart block. In this study, we demonstrate that besides the maternal MHC controlling Ab specificity, fetal MHC-encoded genes influence fetal susceptibility to congenital heart block. Using MHC congenic rat strains, we show that heart block develops in rat pups of three strains carrying MHC haplotype RT1(av1) (DA, PVG.AV1, and LEW.AV1) after maternal Ro52 immunization, but not in LEW rats (RT1(l)). Different anti-Ro52 Ab fine specificities were generated in RT1(av1) versus RT1(l) animals. Maternal and fetal influence was determined in an F(2) cross between LEW.AV1 and LEW strains, which revealed higher susceptibility in RT1(l) than RT1(av1) pups once pathogenic Ro52 Abs were present. This was further confirmed in that RT1(l) pups more frequently developed heart block than RT1(av1) pups after passive transfer of RT1(av1) anti-Ro52 sera. Our findings show that generation of pathogenic Ro52 Abs is restricted by maternal MHC, whereas the fetal MHC locus regulates susceptibility and determines the fetal disease outcome in anti-Ro52-positive pregnancies.
Authors:
Linn S Strandberg; Aurelie Ambrosi; Maja Jagodic; Vijole Dzikaite; Peter Janson; Mohsen Khademi; Stina Salomonsson; Lars Ottosson; Robert Klauninger; Ulrika Adén; Sven-Erik Sonesson; Maria Sunnerhagen; Katrien L de Graaf; Vijay K Kuchroo; Adnane Achour; Ola Winqvist; Tomas Olsson; Marie Wahren-Herlenius
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-08-09
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-03     Completed Date:  2010-11-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3574-82     Citation Subset:  AIM; IM    
Affiliation:
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Antibody Specificity / genetics
Atrioventricular Block / congenital,  genetics*,  immunology*
Autoantibodies / biosynthesis*
Cell Line
Disease Models, Animal
Female
Genetic Predisposition to Disease*
Histocompatibility Antigens / genetics*,  immunology
Maternal-Fetal Exchange / genetics,  immunology*
Molecular Sequence Data
Pregnancy
Rats
Rats, Inbred Lew
Ribonucleoproteins / administration & dosage,  immunology*
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Histocompatibility Antigens; 0/Ribonucleoproteins; 0/SS-A antigen; 0/histocompatibility antigens RT, rat

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