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Year: 2008 Volume: 153 Issue: Supplementary 1

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Genetic imprinting of autoantibody repertoires in systemic lupus erythematosus patients.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Silverman, G. J. Srikrishnan, R. Germar, K. Goodyear, C. S. Andrews, K. A. Ginzler, E. M. Tsao, B. P.
Description	Country affiliation: United States Author Affiliation: Silverman GJ ( Rheumatic Diseases Core Center and the Laboratory of B-cell Immunobiology, University of California, San Diego, CA 92093-0663, USA gsilverman@ucsd.edu)
Abstract	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.
File Format	HTM / HTML
ISSN	00099104
e-ISSN	13652249
DOI	10.1111/j.1365-2249.2008.03680.x
Journal	Clinical & Experimental Immunology
Issue Number	1
Volume Number	153
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2008-07-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Immunology Autoantibodies Genomic Imprinting Lupus Erythematosus, Systemic Genetics Immunology Autoantigens Immunoglobulin G Immunoglobulin M Immunosuppressive Agents Therapeutic Use Drug Therapy Oligonucleotide Array Sequence Analysis Proteomics Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Twin Study
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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