Antibodies against M-Type Phospholipase A2 Receptor May Predict Treatment Response and Outcome in Membranous Nephropathy

Am J Nephrol. 2018;48(6):438-446. doi: 10.1159/000494662. Epub 2018 Nov 23.

Abstract

Background: Anti-phospholipase A2 receptor (PLA2R) antibodies are specific to the diagnosis of primary membranous nephropathy (pMN). The prevalence of positive antibodies varies among different cohorts. Still there is discrepancy in regard to the association between antibody levels and clinical courses, and the prognostic value of antibodies to treatment responses and kidney outcomes.

Methods: Three hundred fifty-nine consecutive kidney biopsy-proven pMN patients were enrolled. Anti-PLA2R antibodies were detected by immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA).

Results: The positive rate of anti-PLA2R antibodies in pMN was 65.2% (234/359) by IFA and 56.3% (202/359) by ELISA. The antibody level presented positive correlation with urinary protein excretion (r = 0.164, p = 0.002). Detectable antibodies and a higher level of proteinuria were independent risk factors to no-remission after treatments (OR 3.15, p = 0.004; OR 1.11, p = 0.006) and were independent risk factors to no-spontaneous remission (OR 2.20, p = 0.011; OR 1.36, p < 0.001). A higher level of antibodies (hazard ratio 1.002, p = 0.019) was the independent risk factor to kidney dysfunction during follow-up. The antibodies turned negative in 42 out of 52 (80.8%) patients who achieved clinical remission, while they remained positive in all patients of the no-response category (p < 0.001).

Conclusion: We documented correlations between anti-PLA2R antibody levels and clinical severity in this large Chinese pMN cohort. Antibody positivity and higher antibody level might predict treatment responses and kidney outcomes of pMN.

Keywords: Antibody; Biomarker; Membranous nephropathy; Phospholipase A2 receptor; Risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Biopsy
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranous / blood
  • Glomerulonephritis, Membranous / diagnosis*
  • Glomerulonephritis, Membranous / drug therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / pathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Receptors, Phospholipase A2 / immunology*
  • Severity of Illness Index*
  • Thrombospondins / immunology
  • Treatment Outcome

Substances

  • Autoantibodies
  • Biomarkers
  • Immunosuppressive Agents
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2
  • THSD7A protein, human
  • Thrombospondins