Characterization of autoantibodies in primary membranous nephropathy and their clinical significance

Expert Rev Clin Immunol. 2019 Feb;15(2):165-175. doi: 10.1080/1744666X.2019.1548934. Epub 2018 Nov 27.

Abstract

Introduction: Membranous nephropathy (MN) is the most common cause of a nephrotic syndrome in Caucasian adults. The identification of target antigens in MN in the last decade has had a major impact on the clinical approach to these patients. Areas covered: Since the discoveries in animal models in the 1980s that circulating autoantibodies induce disease upon in situ binding to glomerular podocytes, many attempts have been undertaken to define the human antigens responsible for disease induction. Only in 2009 was Phospholipase A2 Receptor 1 described as the major antigen responsible for MN onset in about 70% of patients. Subsequently, in 2014, Thrombospondin Type-1 Domain-Containing 7A was identified as a second antigen, accounting for 2-3% of patients with MN. The knowledge of the role of these antibodies in MN has improved the diagnosis and management of patients and helped to better define the need for immunosuppressive treatment. Expert commentary: These discoveries over the last 10 years in the discipline of nephrology have clearly shown the improvements a better understanding of disease pathogenesis can bring for patient care.

Keywords: Membranous nephropathy; immunopathology-driven treatment; malignancy-associated membranous nephropathy; pathogenesis-based biomarkers; phospholipase A receptor 1; thrombospondin Type-1 domain-containing 7A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Epitopes
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / immunology*
  • Glomerulonephritis, Membranous / pathology*
  • Glomerulonephritis, Membranous / therapy
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney / metabolism
  • Kidney / pathology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Receptors, Phospholipase A2 / chemistry
  • Receptors, Phospholipase A2 / immunology*
  • Receptors, Phospholipase A2 / metabolism
  • Thrombospondins / immunology*
  • Thrombospondins / metabolism

Substances

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