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Anticuerpos anti-receptor de fosfolipasa A2 como biomarcador
de nefropatía membranosa
Diego Halabí RoblesPrograma Doctorado en Ciencias Médicas
Nefropatía membranosa
• Enfermedad glomerular mediada por anticuerpos
• Mayor causa de sindrome nefrótico en adultos
• Formación complejos inmunes subepiteliales + activación de complemento = proteinuria
• Heterogeneidad de NM y biomarcadores poco replicables
Beck & Salant (2010)
M-type phospholipase A2 receptor (PLA2R)
C-R: cysteine-rich domainFNII: fibronectin type II domainCTLD: C-type lectin-like domain
Rees & Kain (2009)
Hofstra et al. (2011)
Anti-Phospholipase A2 Receptor Antibodies Correlate with Clinical Status in Idiopathic Membranous Nephropathy
Creatininaβ2mAlbuminaIgGTransferrinaβ-1-micro- globulina
Creatinina séricaAlbuminaColesterolβ2mIgGTransferrina
Síndrome nefrótico Albúmina sérica <3.0 g/dl; proteinuria >3.5 g/d
Remisión espontáneaReducción de proteinuria >50% con proteinuria <3.5 g/d, sin tratamiento inmunosupresor
Remisión inducida por tratamiento
Reducción de proteinuria >50% con proteinuria <3.5 g/d después de tratamiento inmunosupresor
Proteinuria persistente Proteinuria >3.5 g/d o reducción de proteinuria <50%
Relapso Proteinuria >3.5 g/d después de una remisión
Hofstra et al. (2011)
Anti-Phospholipase A2 Receptor Antibodies Correlate with Clinical Status in Idiopathic Membranous Nephropathy
Hofstra et al. (2011)
Hofstra et al. (2011)
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy
Qin et al., 2011
Lupus-MN
HBV-MN
Tumor-associated MN
Indirect immunofluorescence test (IIFT)Hoxha et al., 2011
An immunofluorescence test for phospholipase-A2-receptor antibodies and its clinical usefulness in patients with membranous
glomerulonephritis
Hoxha et al., 2011
Conclusiones• Anti-PLA2R parece ser un biomarcador fiable en
NM
• No es un marcador del curso de la enfermedad, sino de la fase inmunológica
• Es necesario implementar y validar test para diagnósticar NM basado en anticuerpos anti-PLA2R
• Esto eviataría el diagnóstico por biopsia, además de permitir monitorear la enfermedad
Referencias• Beck, L.H. & Salant, D.J., 2010. Membranous nephropathy: recent travels and new
roads ahead. Kidney international, 77(9), pp.765–70.
• Debiec, H. & Ronco, P., 2011. Nephrotic syndrome: A new specific test for idiopathic membranous nephropathy. Nature reviews. Nephrology, 7(9), pp.496–8.
• Hofstra, J.M. et al., 2011. Anti-phospholipase A₂ receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clinical journal of the American Society of Nephrology : CJASN, 6(6), pp.1286–91.
• Hoxha, E. et al., 2011. An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 26(8), pp.2526–32.
• Qin, W. et al., 2011. Anti-phospholipase A2 receptor antibody in membranous nephropathy. Journal of the American Society of Nephrology : JASN, 22(6), pp.1137–43.