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dc.contributor.authorSilverman, G J
dc.contributor.authorSrikrishnan, R
dc.contributor.authorGermar, K
dc.contributor.authorGoodyear, C S
dc.contributor.authorAndrews, K A
dc.contributor.authorGinzler, E M
dc.contributor.authorTsao, B P
dc.date.accessioned2023-02-03T18:00:23Z
dc.date.available2023-02-03T18:00:23Z
dc.date.issued2008-05-28
dc.identifier.citationSilverman GJ, Srikrishnan R, Germar K, Goodyear CS, Andrews KA, Ginzler EM, Tsao BP. Genetic imprinting of autoantibody repertoires in systemic lupus erythematosus patients. Clin Exp Immunol. 2008 Jul;153(1):102-16. doi: 10.1111/j.1365-2249.2008.03680.x. Epub 2008 May 28. PMID: 18510544; PMCID: PMC2432104.en_US
dc.identifier.eissn1365-2249
dc.identifier.doi10.1111/j.1365-2249.2008.03680.x
dc.identifier.pmid18510544
dc.identifier.urihttp://hdl.handle.net/20.500.12648/8239
dc.description.abstractSystemic 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.
dc.language.isoenen_US
dc.relation.urlhttps://academic.oup.com/cei/article/153/1/102/6457473en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleGenetic imprinting of autoantibody repertoires in systemic lupus erythematosus patients.en_US
dc.typeArticle/Reviewen_US
dc.source.journaltitleClinical and experimental immunologyen_US
dc.source.volume153
dc.source.issue1
dc.source.beginpage102
dc.source.endpage16
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryEngland
dc.description.versionVoRen_US
refterms.dateFOA2023-02-03T18:00:24Z
html.description.abstractSystemic 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.
dc.description.institutionSUNY Downstateen_US
dc.description.departmentRheumatologyen_US
dc.description.degreelevelN/Aen_US
dc.identifier.journalClinical and experimental immunology


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