Podocyte Injury in Membranous and Proliferative Lupus Nephritis: Distinct Underlying Mechanisms?

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorREZENDE, Gabriela M.
dc.contributor.authorVIANA, Vilma S. T.
dc.contributor.authorMALHEIROS, Denise M.
dc.contributor.authorLEON, Elaine P.
dc.contributor.authorBORBA, Eduardo F.
dc.contributor.authorSILVA, Neila A. S.
dc.contributor.authorNORONHA, Irene L.
dc.contributor.authorSILVA, Cleonice
dc.contributor.authorBONFA, Eloisa
dc.date.accessioned2013-10-11T21:25:41Z
dc.date.available2013-10-11T21:25:41Z
dc.date.issued2012
dc.description.abstractBackground/Purpose: Lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) with proteinuria being the predominant common manifestation and may therefore reflect podocyte injury. Podocytes are highly specialized cells that have a relevant role in the glomerular filtration barrier and alteration in the expression of their biomarkers has been shown to be associated with podocyte dysfunction in some glomerulopathies. A systematic analysis of podocyte-associated molecules encom-passing different subcellular compartments was performed in a large series of LN biopsies. Expression of Wilms tumor protein (WT1), Synaptopodin (Synpo) and glomerular epithelial protein 1 (GLEPP1) with nuclear, cytoplasmic and membrane distribution respectively, were evaluated attempting to identify if podocyte phenotype is distinct in proliferative and membranous nephritis. Possible association of molecular expression alterations with long term proteinuria severity and outcome in lupus was also investigated. Methods: Immunohistochemistry analysis was performed using monoclonal antibodies to WT1, Synpo and GLEPP1 proteins in 52 biopsies from patients with lupus nephritis fulfilling the revised ACR criteria for SLE. Demographic, clinical and laboratorial data at the time of biopsy were analyzed. Results: Thirty-nine (75%) biopsies were classified as proliferative LN and thirteen (25%) as pure membranous class V. Immunohistochemistry analysis in normal kidney revealed preserved staining of WT1, Synpo and GLEPP1 podocyte biomarkers along the capillary walls. Preserved and concomitant WT1 and Synpo staining was observed in a significant higher frequency in pure class V biopsies than in proliferative LN (69.23 vs. 2.56%, p 0.0001). Likewise, preserved GLEPP1 expression was also more frequent in pure class V LN (53.85 vs. 2.86%, p 0.0002). Proteinuria and serum albumin levels at the time of biopsy did not statistically differ in the two groups (p 0.87 and p 0.41) whereas in the mean long-term follow-up of four years a tendency of lower proteinuria (p 0.050) was observed in those patients with biopsies expressing preserved WT1/Synpo staining. Conclusion: This is the first study comparing proliferative and membranous lupus nephritis which evaluated simultaneously the expression of proteins in different subcellular podocyte compartments and provided novel evidence of preserved podocyte structural architecture predominantly in membranous lesions which may account for a better long term outcome of patients with this LN histological class. These findings suggest possible different underlying mechanisms for proteinuria in both conditions.
dc.description.conferencedateNOV 09-14, 2012
dc.description.conferencelocalWashington - DC, EUA
dc.description.conferencenameAnnual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP)
dc.description.indexMEDLINE
dc.identifier.citationARTHRITIS AND RHEUMATISM, v.64, n.10, suppl.S, p.S1055-S1056, 2012
dc.identifier.issn0004-3591
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/2990
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.relation.ispartofArthritis and Rheumatism
dc.rightsrestrictedAccess
dc.rights.holderCopyright WILEY-BLACKWELL
dc.subject.wosRheumatology
dc.titlePodocyte Injury in Membranous and Proliferative Lupus Nephritis: Distinct Underlying Mechanisms?
dc.typeconferenceObject
dc.type.categorymeeting abstract
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.contributor.author-fmusphcGABRIELA DE MENDONCA REZENDE
hcfmusp.contributor.author-fmusphcVILMA DOS SANTOS TRINDADE VIANA
hcfmusp.contributor.author-fmusphcDENISE MARIA AVANCINI COSTA MALHEIROS
hcfmusp.contributor.author-fmusphcELAINE PIRES LEON
hcfmusp.contributor.author-fmusphcEDUARDO FERREIRA BORBA NETO
hcfmusp.contributor.author-fmusphcNEILA APARECIDA DE SOUZA SILVA
hcfmusp.contributor.author-fmusphcIRENE DE LOURDES NORONHA
hcfmusp.contributor.author-fmusphcCLEONICE DA SILVA
hcfmusp.contributor.author-fmusphcELOISA SILVA DUTRA DE OLIVEIRA BONFA
hcfmusp.description.beginpageS1055
hcfmusp.description.endpageS1056
hcfmusp.description.issue10
hcfmusp.description.issuesuppl S
hcfmusp.description.volume64
hcfmusp.origemWOS
hcfmusp.origem.wosWOS:000309748306010
hcfmusp.publisher.cityHOBOKEN
hcfmusp.publisher.countryUSA
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Coleções
Comunicações em Eventos - FM/MCM
Comunicações em Eventos - HC/ICHC
Comunicações em Eventos - LIM/16
Comunicações em Eventos - LIM/17
Comunicações em Eventos - LIM/29