Document Detail


Familial aggregation and linkage analysis of autoantibody traits in pedigrees multiplex for systemic lupus erythematosus.
MedLine Citation:
PMID:  16775618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Autoantibodies are clinically relevant biomarkers for numerous autoimmune disorders. The genetic basis of autoantibody production in systemic lupus erythematosus (SLE) and other autoimmune diseases is poorly understood. In this study, we characterized autoantibody profiles in 1,506 individuals from 229 multiplex SLE pedigrees. There was strong familial aggregation of antinuclear antibodies (ANAs), anti-double-stranded DNA (dsDNA), anti-La/SSB, anti-Ro/SSA, anti-Sm, anti-nRNP (nuclear ribonucleoprotein), IgM antiphospholipid (aPL) antibodies (Abs) and rheumatoid factor (RF) across these families enriched for lupus. We performed genome-wide linkage analyses in an effort to map genes that contribute to the production of the following autoantibodies: Ro/SSA, La/SSB, nRNP, Sm, dsDNA, RF, nuclear and phospholipids. Using an approach to minimize false positives and adjust for multiple comparisons, evidence for linkage was found to anti-La/SSB Abs on chromosome 3q21 (adjusted P=1.9 x 10(-6)), to anti-nRNP and/or anti-Sm Abs on chromosome 3q27 (adjusted P=3.5 x 10(-6)), to anti-Ro/SSA and/or anti-La/SSB Abs on chromosome 4q34-q35 (adjusted P=3.4 x 10(-4)) and to anti-IgM aPL Abs on chromosome 13q14 (adjusted P=2.3 x 10(-4)). These results support the hypothesis that autoantibody production is a genetically complex trait. Identification of the causative alleles will advance our understanding of critical molecular mechanisms that underlie SLE and perhaps other autoimmune diseases.
Authors:
P S Ramos; J A Kelly; C Gray-McGuire; G R Bruner; A N Leiran; C M Meyer; B Namjou; K J Espe; W A Ortmann; M Reichlin; C D Langefeld; J A James; P M Gaffney; T W Behrens; J B Harley; K L Moser
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-06-15
Journal Detail:
Title:  Genes and immunity     Volume:  7     ISSN:  1466-4879     ISO Abbreviation:  Genes Immun.     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-07-26     Completed Date:  2006-09-14     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100953417     Medline TA:  Genes Immun     Country:  England    
Other Details:
Languages:  eng     Pagination:  417-32     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Data Bank Information
Bank Name/Acc. No.:
OMIM/152700
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MeSH Terms
Descriptor/Qualifier:
African Americans
Antibodies, Antinuclear / blood
Autoantibodies / blood,  classification,  genetics*
Autoimmune Diseases / genetics
Biological Markers / blood
Case-Control Studies
Chromosome Mapping
Chromosomes, Human, Pair 13
Chromosomes, Human, Pair 3
Chromosomes, Human, Pair 4
European Continental Ancestry Group
Female
Genetic Predisposition to Disease
Humans
Linkage (Genetics)*
Lupus Erythematosus, Systemic / genetics*,  immunology*
Male
Pedigree*
Grant Support
ID/Acronym/Agency:
AI053747/AI/NIAID NIH HHS; AI24717/AI/NIAID NIH HHS; AI31584/AI/NIAID NIH HHS; AR048940/AR/NIAMS NIH HHS; AR42460/AR/NIAMS NIH HHS; AR46405/AR/NIAMS NIH HHS; N01 AR12253/AR/NIAMS NIH HHS; RR020143/RR/NCRR NIH HHS; RR03655/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Autoantibodies; 0/Biological Markers

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