title: Prevalence, diagnostic value and clinical characteristics associated with the presence of circulating levels and renal deposits of antibodies against the M-type phospholipase A2 receptor in idiopathic membranous nephropathy.
abstract: The M-type phospholipase A2 receptor (PLA2R) has been identified as one of the target antigens of the autoimmune response in idiopathic membranous nephropathy (MN). The prevalence of anti-PLA2R antibodies in patients with idiopathic MN is around 70% but this varies in accordance with geographic region, and until present, anti-PLA2R has not been shown to be associated with any particular clinical profile of the disease.
  
  
  METHODS
  We studied 64 adults with nephrotic syndrome who were diagnosed with MN, confirmed by renal biopsy. Forty-seven patients had idiopathic MN and 17 had secondary MN. We determined the presence of circulating anti-PLA2R antibodies by indirect immunofluorescence (IIF) and their titre by ELISA, and we analysed the presence of anti-PLA2R antibody renal deposits by immunohistochemical techniques. We calculated the sensitivity and specificity of the IIF and ELISA techniques for the identification of patients with renal deposits and for the identification of those with idiopathic MN and we tested whether there were differences in the clinical profile of the disease at the time of diagnosis according to the presence or absence of anti-PLA2R antibodies.
  
  
  RESULTS
  We did not observe significant differences in the clinical-demographic variables between patients with idiopathic and secondary MN. The prevalence of anti-PLA2R glomerular deposits by IHC was 76.6%. The IIF and ELISA techniques had a similar sensitivity (IIF 94.4% and ELISA 97.2%) and specificity (100%) for the identification of patients with anti-PLA2R renal deposits and the detection of circulating anti-PLA2R antibodies. The determination of anti-PLA2R by IIF identified patients with idiopathic MN with a sensitivity of 72.3% and a specificity of 94.2%. A titre of antibodies >15RU/ml measured by ELISA had a sensitivity of 74.45% and a specificity of 94.2% for the identification of patients with idiopathic MN. Patients with idiopathic MN and anti-PLA2R had significantly higher proteinuria figures (13.25 [P25-P75: 9.05-15.87] compared to 9.43 [P25-P75: 6.30-15] g/day, P:.018). No statistical correlation was observed between the antibody titre measured by ELISA and age, glomerular filtration rate or 24-hour proteinuria or albuminaemia.
  
  
  CONCLUSIONS
  The techniques employed to determine anti-PLA2R in patients with MN are highly specific for the diagnosis of idiopathic forms of the glomerular disease. The frequency with which patients with MN and anti-PLA2R were identified is similar to that reported in previous studies. Staining by immunohistochemistry is the most sensitive method for detecting cases of MN associated with the presence of anti-PLA2R antibodies. The IIF and ELISA techniques allow circulating anti-PLA2R antibodies to be detected in most patients with renal deposits, but they may very infrequently have false negative results. The concordance of these tests is high. Patients with idiopathic MN and anti-PLA2R antibody renal deposits have higher proteinuria than patients that are anti-PLA2R negative, but the differences have little clinical importance.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Segarra-Medrano
authors.forename: Elías
authors.initials: E
authors.lastname: Jatem-Escalante
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Quiles-Pérez
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Salcedo
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Arbós-Via
authors.forename: Helena
authors.initials: H
authors.lastname: Ostos
authors.forename: Naiara
authors.initials: N
authors.lastname: Valtierra
authors.forename: Clara
authors.initials: C
authors.lastname: Carnicer-Cáceres
authors.forename: Irene
authors.initials: I
authors.lastname: Agraz-Pamplona
mesh_terms: D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D000090266:Chromobox Protein Homolog 5; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007668:Kidney / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D054507:Receptors, Phospholipase A2 / Q000145:classification / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C000715594:CBX5 protein, human; D054507:Receptors, Phospholipase A2; D000090266:Chromobox Protein Homolog 5