A Proposal for a Serology-Based Approach to Membranous Nephropathy

J Am Soc Nephrol. 2017 Feb;28(2):421-430. doi: 10.1681/ASN.2016070776. Epub 2016 Oct 24.


Primary membranous nephropathy (MN) is an autoimmune disease mainly caused by autoantibodies against the recently discovered podocyte antigens: the M-type phospholipase A2 receptor 1 (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Assays for quantitative assessment of anti-PLA2R antibodies are commercially available, but a semiquantitative test to detect anti-THSD7A antibodies has been only recently developed. The presence or absence of anti-PLA2R and anti-THSD7A antibodies adds important information to clinical and immunopathologic data in discriminating between primary and secondary MN. Levels of anti-PLA2R antibodies and possibly, anti-THSD7A antibodies tightly correlate with disease activity. Low baseline and decreasing anti-PLA2R antibody levels strongly predict spontaneous remission, thus favoring conservative therapy. Conversely, high baseline or increasing anti-PLA2R antibody levels associate with nephrotic syndrome and progressive loss of kidney function, thereby encouraging prompt initiation of immunosuppressive therapy. Serum anti-PLA2R antibody profiles reliably predict response to therapy, and levels at completion of therapy may forecast long-term outcome. Re-emergence of or increase in antibody titers precedes a clinical relapse. Persistence or reappearance of anti-PLA2R antibodies after kidney transplant predicts development of recurrent disease. We propose that an individualized serology-based approach to MN, used to complement and refine the traditional proteinuria-driven approach, will improve the outcome in this disease.

Keywords: Immunology and pathology; PLA2R; THSD7A; clinical nephrology; membranous nephropathy.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Autoantibodies / blood
  • Glomerulonephritis, Membranous / blood*
  • Glomerulonephritis, Membranous / diagnosis*
  • Glomerulonephritis, Membranous / therapy
  • Humans
  • Kidney Transplantation
  • Prognosis
  • Receptors, Phospholipase A2 / immunology
  • Serologic Tests


  • Autoantibodies
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2