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Article: Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake

TitleCopy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake
Authors
Issue Date2008
PublisherRockefeller University Press. The Journal's web site is located at http://www.jem.org
Citation
Journal Of Experimental Medicine, 2008, v. 205 n. 7, p. 1573-1582 How to Cite?
AbstractCopy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcγRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcγRIIIb- deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcγRIIIb. Reduced FcyRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.
Persistent Identifierhttp://hdl.handle.net/10722/57550
ISSN
2015 Impact Factor: 11.24
2015 SCImago Journal Rankings: 10.762
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Wellcome Trust Clinician Research Leave Award
Medical Research Council (MRC)
Kidney Research UK (KRUK)
Genzyme Renal Innovations Programme
national Institute for Health Research Cambridge Biomedical Research Centre
Arthritis Research Campaign
University of Manchester
Funding Information:

We thank Dr. Tom Freeman for contribution to array development; Drs. Kevin Harris, David Jayne, and Afzal Chaudhry for clinical input; and Dr. Chaudhry for statistical advice. We are grateful to all the patients involved in the study, but in particular for the generous contribution to this research made by our Fc gamma RIIIb-deficient patient and her family. We also acknowledge Dr. Dawn L. Cooper's contribution to the flow cytometry data.

References

 

DC FieldValueLanguage
dc.contributor.authorWillcocks, LCen_HK
dc.contributor.authorLyons, PAen_HK
dc.contributor.authorClatworthy, MRen_HK
dc.contributor.authorRobinson, JIen_HK
dc.contributor.authorYang, Wen_HK
dc.contributor.authorNewland, SAen_HK
dc.contributor.authorPlagnol, Ven_HK
dc.contributor.authorMcGovern, NNen_HK
dc.contributor.authorCondliffe, AMen_HK
dc.contributor.authorChilvers, ERen_HK
dc.contributor.authorAdu, Den_HK
dc.contributor.authorJolly, ECen_HK
dc.contributor.authorWatts, Ren_HK
dc.contributor.authorLau, YLen_HK
dc.contributor.authorMorgan, AWen_HK
dc.contributor.authorNash, Gen_HK
dc.contributor.authorSmith, KGCen_HK
dc.date.accessioned2010-04-12T01:39:51Z-
dc.date.available2010-04-12T01:39:51Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Experimental Medicine, 2008, v. 205 n. 7, p. 1573-1582en_HK
dc.identifier.issn0022-1007en_HK
dc.identifier.urihttp://hdl.handle.net/10722/57550-
dc.description.abstractCopy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcγRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcγRIIIb- deficiency and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcγRIIIb. Reduced FcyRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes, which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus, we define a role for FCGR3B CNV in immune complex clearance, a function that may explain why low FCGR3B CNV is associated with SLE, but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.en_HK
dc.languageengen_HK
dc.publisherRockefeller University Press. The Journal's web site is located at http://www.jem.orgen_HK
dc.relation.ispartofJournal of Experimental Medicineen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe Journal of Experimental Medicine. Copyright © Rockefeller University Press.en_HK
dc.subject.meshAntigen-Antibody Complex - genetics - immunologyen_HK
dc.subject.meshGene Expression Regulation - genetics - immunologyen_HK
dc.subject.meshGene Dosage - genetics - immunologyen_HK
dc.subject.meshGenetic Predisposition to Diseaseen_HK
dc.subject.meshGenetic Variation - immunologyen_HK
dc.titleCopy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptakeen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-1007&volume=205&issue=7&spage=1573&epage=1582&date=2008&atitle=Copy+number+of+FCGR3B,+which+is+associated+with+systemic+lupus+erythematosus,+correlates+with+protein+expression+and+immune+complex+uptakeen_HK
dc.identifier.emailYang, W:yangwl@hkucc.hku.hken_HK
dc.identifier.emailLau, YL:lauylung@hkucc.hku.hken_HK
dc.identifier.authorityYang, W=rp00524en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1084/jem.20072413en_HK
dc.identifier.pmid18559452-
dc.identifier.pmcidPMC2442635en_HK
dc.identifier.scopuseid_2-s2.0-46949096094en_HK
dc.identifier.hkuros145090-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-46949096094&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume205en_HK
dc.identifier.issue7en_HK
dc.identifier.spage1573en_HK
dc.identifier.epage1582en_HK
dc.identifier.isiWOS:000258527000010-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001115317-
dc.identifier.scopusauthoridWillcocks, LC=24464597300en_HK
dc.identifier.scopusauthoridLyons, PA=7102522977en_HK
dc.identifier.scopusauthoridClatworthy, MR=6701499712en_HK
dc.identifier.scopusauthoridRobinson, JI=26326507700en_HK
dc.identifier.scopusauthoridYang, W=23101349500en_HK
dc.identifier.scopusauthoridNewland, SA=16402784900en_HK
dc.identifier.scopusauthoridPlagnol, V=16402494600en_HK
dc.identifier.scopusauthoridMcGovern, NN=23974751600en_HK
dc.identifier.scopusauthoridCondliffe, AM=6603324383en_HK
dc.identifier.scopusauthoridChilvers, ER=7006017543en_HK
dc.identifier.scopusauthoridAdu, D=7004332208en_HK
dc.identifier.scopusauthoridJolly, EC=16304380800en_HK
dc.identifier.scopusauthoridWatts, R=7401740971en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.scopusauthoridMorgan, AW=7403138399en_HK
dc.identifier.scopusauthoridNash, G=7101646933en_HK
dc.identifier.scopusauthoridSmith, KGC=7410186181en_HK
dc.identifier.citeulike3075585-

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