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Article: Mesangial cell-binding anti-DNA antibodies in patients with systemic lupus erythematosus

TitleMesangial cell-binding anti-DNA antibodies in patients with systemic lupus erythematosus
Authors
Issue Date2002
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Journal Of The American Society Of Nephrology, 2002, v. 13 n. 5, p. 1219-1229 How to Cite?
AbstractThe mechanisms by which anti-DNA antibodies contribute to the pathogenesis of lupus nephritis (LN) remain to be elucidated. This study investigates the binding of polyclonal anti-DNA immunoglobulins from patients with systemic lupus erythematosus (SLE) to human mesangial cells (HMC) in vitro. Testing of cross-sectional serum samples from 280 LN patients (108 during active disease; 172 during remission), 35 SLE patients without renal involvement, 72 patients with nonlupus primary glomerular diseases, and 37 healthy subjects with a cellular enzyme-linked immunosorbent assay showed significant IgG mesangial cell-binding activity in patients with SLE, particularly those with active LN (P < 0.0001). Significant HMC-binding activity was demonstrated in 83.9%, 42.8%, and 47.1% of patients with active LN, inactive LN, and non-renal SLE, respectively. This was predominantly attributed to binding by anti-DNA antibodies, and immune complex binding accounted for 4.6%, 3.5%, and 2.8% of seropositive samples in the respective groups. Longitudinal studies in 27 LN patients demonstrated correlation between serial levels of anti-DNA antibodies, serum HMC-binding activity, and disease activity in 18 patients (66.7%). Affinity-purified polyclonal IgG anti-DNA antibodies from sera with HMC-binding activity showed significant binding to cultured HMC, and to a lesser extent glomerular and proximal tubular epithelial cells and human umbilical vein endothelial cells, but not tumor cell lines, peritoneal mesothelial cells, bronchial epithelial cells, or fibroblasts. The binding of anti-DNA antibodies to HMC was increased 1.47-fold (P = 0.0059) after the removal of Ig-associated DNA by DNase treatment, but it was unaffected by DNase treatment of HMC membrane. Controlled trypsinization of membrane proteins in HMC resulted in a 1.26-fold (P = 0.0025) increase in their binding by anti-DNA antibodies. In conclusion, subsets of anti-DNA antibodies from patients with SLE are capable of binding to HMC. The association of such binding with renal involvement and disease activity and its modulation by DNA concentration suggest that Ig binding to HMC can be a potential marker for disease activity in selected patients and that the binding of anti-DNA antibodies to HMC may be a pathogenetic mechanism in LN.
Persistent Identifierhttp://hdl.handle.net/10722/77045
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TMen_HK
dc.contributor.authorLeung, JKHen_HK
dc.contributor.authorHo, SKNen_HK
dc.contributor.authorYung, Sen_HK
dc.date.accessioned2010-09-06T07:27:41Z-
dc.date.available2010-09-06T07:27:41Z-
dc.date.issued2002en_HK
dc.identifier.citationJournal Of The American Society Of Nephrology, 2002, v. 13 n. 5, p. 1219-1229en_HK
dc.identifier.issn1046-6673en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77045-
dc.description.abstractThe mechanisms by which anti-DNA antibodies contribute to the pathogenesis of lupus nephritis (LN) remain to be elucidated. This study investigates the binding of polyclonal anti-DNA immunoglobulins from patients with systemic lupus erythematosus (SLE) to human mesangial cells (HMC) in vitro. Testing of cross-sectional serum samples from 280 LN patients (108 during active disease; 172 during remission), 35 SLE patients without renal involvement, 72 patients with nonlupus primary glomerular diseases, and 37 healthy subjects with a cellular enzyme-linked immunosorbent assay showed significant IgG mesangial cell-binding activity in patients with SLE, particularly those with active LN (P < 0.0001). Significant HMC-binding activity was demonstrated in 83.9%, 42.8%, and 47.1% of patients with active LN, inactive LN, and non-renal SLE, respectively. This was predominantly attributed to binding by anti-DNA antibodies, and immune complex binding accounted for 4.6%, 3.5%, and 2.8% of seropositive samples in the respective groups. Longitudinal studies in 27 LN patients demonstrated correlation between serial levels of anti-DNA antibodies, serum HMC-binding activity, and disease activity in 18 patients (66.7%). Affinity-purified polyclonal IgG anti-DNA antibodies from sera with HMC-binding activity showed significant binding to cultured HMC, and to a lesser extent glomerular and proximal tubular epithelial cells and human umbilical vein endothelial cells, but not tumor cell lines, peritoneal mesothelial cells, bronchial epithelial cells, or fibroblasts. The binding of anti-DNA antibodies to HMC was increased 1.47-fold (P = 0.0059) after the removal of Ig-associated DNA by DNase treatment, but it was unaffected by DNase treatment of HMC membrane. Controlled trypsinization of membrane proteins in HMC resulted in a 1.26-fold (P = 0.0025) increase in their binding by anti-DNA antibodies. In conclusion, subsets of anti-DNA antibodies from patients with SLE are capable of binding to HMC. The association of such binding with renal involvement and disease activity and its modulation by DNA concentration suggest that Ig binding to HMC can be a potential marker for disease activity in selected patients and that the binding of anti-DNA antibodies to HMC may be a pathogenetic mechanism in LN.en_HK
dc.languageengen_HK
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.orgen_HK
dc.relation.ispartofJournal of the American Society of Nephrologyen_HK
dc.rightsJournal of the American Society of Nephrology. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subject.meshAdulten_HK
dc.subject.meshAntibodies, Antinuclear - blood - immunologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCross-Sectional Studiesen_HK
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshFlow Cytometryen_HK
dc.subject.meshGlomerular Mesangium - immunologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunoglobulin G - immunologyen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshLongitudinal Studiesen_HK
dc.subject.meshLupus Erythematosus, Systemic - blood - immunologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshProtein Bindingen_HK
dc.subject.meshStatistics, Nonparametricen_HK
dc.titleMesangial cell-binding anti-DNA antibodies in patients with systemic lupus erythematosusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1046-6673&volume=13&issue=5&spage=1219&epage=1229&date=2002&atitle=Mesangial+cell-binding+anti-DNA+antibodies+in+patients+with+systemic+lupus+erythematosusen_HK
dc.identifier.emailChan, TM:dtmchan@hku.hken_HK
dc.identifier.emailYung, S:ssyyung@hku.hken_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/01.ASN.0000014223.71109.13en_HK
dc.identifier.pmid11961009en_HK
dc.identifier.scopuseid_2-s2.0-0036232276en_HK
dc.identifier.hkuros67219en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036232276&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume13en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1219en_HK
dc.identifier.epage1229en_HK
dc.identifier.isiWOS:000175210800011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridLeung, JKH=7202180353en_HK
dc.identifier.scopusauthoridHo, SKN=36839065300en_HK
dc.identifier.scopusauthoridYung, S=22636568800en_HK

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