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.