title: Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy.
abstract: BACKGROUND
  Secretory phospholipase A2 receptor (PLA2R) is the target antigen of the auto-antibodies produced in most (∼ 70%) patients with primary membranous nephropathy (pMN). The applicability of anti-PLA2R1 antibody monitoring for the prediction of MN recurrence in kidney transplant recipients still is a matter of debate.
  
  
  METHODS
  We sought to characterize the presence and concentration of anti-PLA2R antibodies by enzyme-linked immunosorbent assay (ELISA) in a cohort of 21 patients with pMN before and after transplantation to evaluate whether anti-PLA2R concentrations could predict pMN recurrence.
  
  
  RESULTS
  The presence of pMN recurrence was significantly correlated with the existence of a positive ELISA assay at graft biopsy or with high level of anti-PLA2R1 activity before transplantation (P = 0.03). In the receiver operating characteristic analysis, anti-PLA2R levels (cut-off of 45 U/mL) during the pretransplantation period accurately predicted pMN recurrence, with a sensitivity of 85.3%, specificity of 85.1%, negative predictive value of 92%, and an area under the curve of 90.8%. This finding supports the hypothesis that anti-PLA2R cause pMN recurrence in humans and indicates the need to prove in an experimental model. Furthermore, 6 of 7 patients with recurrence were carriers of HLA DQA1* 05:01/05 and DQB1* 02:01, confirming these DQ alleles as those associated with higher anti-PLA2R levels.
  
  
  CONCLUSIONS
  This study is the first to demonstrate pretransplantation circulating anti-PLA2R antibodies in a cohort of renal transplant recipients who prospectively developed recurrent disease. Currently, anti-PLA2R levels measured by ELISA may be a rational tool to establish the risk of MN recurrence in renal allograft recipients.
authors: 1 Servicio de Nefrología y Trasplante Renal, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, Spain. 2 Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain. 3 Servicio de Inmunología, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain. 4 Servicio de Inmunología (CDB), Hospital Clinic, Barcelona, Spain. 5 Servicio de Anatomía Patológica, Hospital Universitario Marqués de Valdecilla-IDIVAL, Universidad de Cantabria, Santander, Spain.
authors: Luis F
authors: LF
authors: Quintana
authors: Miquel
authors: M
authors: Blasco
authors: Miguel
authors: M
authors: Seras
authors: Nuria S
authors: NS
authors: Pérez
authors: Marcos
authors: M
authors: López-Hoyos
authors: Patricia
authors: P
authors: Villarroel
authors: Emilio
authors: E
authors: Rodrigo
authors: Odette
authors: O
authors: Viñas
authors: Guadalupe
authors: G
authors: Ercilla
authors: Fritz
authors: F
authors: Diekmann
authors: José J
authors: JJ
authors: Gómez-Roman
authors: Gema
authors: G
authors: Fernandez-Fresnedo
authors: Federico
authors: F
authors: Oppenheimer
authors: Manuel
authors: M
authors: Arias
authors: Josep M
authors: JM
authors: Campistol
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000601:surgery*; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D054507:Receptors, Phospholipase A2 / Q000276:immunology*; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2