Document Detail


Genetic imprinting of autoantibody repertoires in systemic lupus erythematosus patients.
MedLine Citation:
PMID:  18510544     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Systemic lupus erythematosus (SLE) is an autoimmune disease distinguished by great heterogeneity in clinical manifestations and autoantibody expression. While only a handful of autoantibody specificities have proved useful for clinical diagnosis, to characterize complex lupus-associated autoantibody profiles more fully we have applied proteome microarray technology. Our multiplex microarrays included control ligands and 65-autoantigens, which represent diverse nuclear and cytoplasmic antigens recognized by disease-associated and natural autoantibodies. From longitudinal surveys of unrelated SLE patients, we found that autoantibody profile patterns can be patient-specific and highly stable overtime. From profiles of 38 SLE patients that included 14 sets of SLE twins, autoantibodies to the phospholipid neo-determinants, malondialdehyde (MDA) and phosphorylcholine (PC), which are exposed on apoptotic but not healthy cells, were among the most prevalent and highly expressed. We also found that immunoglobulin M (IgM) reactivity to MDA and PC ligands had significant direct correlations with DNA-containing antigens, while such a general relationship was not found with a panel of RNA-related antigens, or for IgG-autoantibodies. Significantly, hierarchical analysis revealed co-distribution/clustering of the IgM autoantibody repertoire patterns for six of 14 twin sets, and such patterns were even more common (10 of 14) for IgG autoantibody profiles. Our findings highlight the potentially distinct roles of IgM and IgG autoantibodies, as we postulate that the direct correlations for IgM autoantibodies to DNA antigens with apoptosis-related determinants may be due to co-expression arising from common pro-homeostatic protective roles. In contrast, the sharing of IgG autoantibody fingerprints by monozygotic twins suggests that lupus IgG autoantibodies can arise in predisposed individuals in genetically determined patterns.
Authors:
G J Silverman; R Srikrishnan; K Germar; C S Goodyear; K A Andrews; E M Ginzler; B P Tsao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Twin Study     Date:  2008-05-28
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  153     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-25     Completed Date:  2008-07-25     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  102-16     Citation Subset:  IM    
Affiliation:
Rheumatic Diseases Core Center and the Laboratory of B-cell Immunobiology, University of California, San Diego, CA 92093-0663, USA gsilverman@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Adult
Autoantibodies / analysis*
Autoantigens / genetics
Female
Genomic Imprinting*
Humans
Immunoglobulin G / immunology
Immunoglobulin M / immunology
Immunosuppressive Agents / therapeutic use
Lupus Erythematosus, Systemic / drug therapy,  genetics*,  immunology*
Middle Aged
Oligonucleotide Array Sequence Analysis
Proteomics
Grant Support
ID/Acronym/Agency:
AI40305/AI/NIAID NIH HHS; AI46637/AI/NIAID NIH HHS; AR43814/AR/NIAMS NIH HHS; AR47360/AR/NIAMS NIH HHS; AR50659/AR/NIAMS NIH HHS; R01 AR043814-11/AR/NIAMS NIH HHS; R01 AR043814-13/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Autoantigens; 0/Immunoglobulin G; 0/Immunoglobulin M; 0/Immunosuppressive Agents
Comments/Corrections

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