title: Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years.
abstract: BACKGROUND
  Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers.
  
  
  METHODS
  In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status.
  
  
  RESULTS
  Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria.
  
  
  CONCLUSIONS
  Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Henri Mondor, Department of Nephrology and Transplantation, Créteil, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Pourcine
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Nephrology and Dialysis, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Dahan
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Nephrology and Dialysis, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Mihout
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Department of Clinical Pharmacology and Unité de Recherche Clinique, Paris, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Cachanado
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Pathology, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brocheriou
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie Univ Paris, Paris, France.|Institut National de la Santé Et la Recheche Médicale, Unit, Paris, France.
authors.forename: Hanna
authors.initials: H
authors.lastname: Debiec
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Department of Nephrology and Dialysis, Paris, France.|Sorbonne Universités, Université Pierre et Marie Curie Univ Paris, Paris, France.|Institut National de la Santé Et la Recheche Médicale, Unit, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D000941:Antigens / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity; D001706:Biopsy; D066246:ErbB Receptors / Q000097:blood; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria / Q000097:blood / Q000276:immunology; D054507:Receptors, Phospholipase A2 / Q000097:blood* / Q000276:immunology; D012709:Serum Albumin / Q000378:metabolism; D019699:Thrombospondins / Q000097:blood / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2; D012709:Serum Albumin; C546399:THSD7A protein, human; D019699:Thrombospondins; C512478:EGFR protein, human; D066246:ErbB Receptors