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Temporal IgG Subtype Changes in Recurrent Idiopathic Membranous Nephropathy.

A G Kattah1, M P Alexander2, A Angioi3

  • 1Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|March 29, 2016
PubMed
Summary

In recurrent membranous nephropathy (MN), the dominant immunoglobulin G (IgG) subtype in kidney deposits typically remains consistent over time, regardless of treatment or phospholipase A2 receptor (PLA2R) association.

Keywords:
clinical research/practiceglomerular biology and diseaseimmune regulationkidney transplantation/nephrologypathology/histopathologyrecurrent disease

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Area of Science:

  • Nephrology
  • Immunology
  • Transplantation

Background:

  • Immunoglobulin G (IgG) subtypes in kidney immune deposits aid in diagnosing membranous nephropathy (MN).
  • Idiopathic and recurrent MN often show predominant IgG4, while secondary MN and de novo disease feature IgG1, IgG2, and IgG3.
  • Temporal changes and clinical correlations of IgG subclasses in individual patients with recurrent MN are not well understood.

Purpose of the Study:

  • To investigate the temporal stability of IgG subtypes in immune deposits in patients with recurrent membranous nephropathy (MN) post-kidney transplantation.
  • To explore the correlation between IgG subtypes, phospholipase A2 receptor (PLA2R) status, and clinical variables in recurrent MN.
  • To assess the impact of rituximab treatment on IgG subtype dominance in recurrent MN.

Main Methods:

  • Retrospective review of 49 kidney biopsies from 18 patients with recurrent MN undergoing transplantation (1998-2013).
  • Performed IgG subtyping (IgG1-4) on kidney biopsies and tested for serum phospholipase A2 receptor (PLA2R) autoantibodies or performed kidney PLA2R antigen staining.
  • Analyzed serial biopsies to assess temporal changes in IgG subtypes and correlated findings with clinical data and treatment.

Main Results:

  • IgG4 was the (co)dominant IgG subtype in 10 of 14 biopsies at recurrence diagnosis, irrespective of PLA2R association.
  • In 8 of 12 transplantations with serial biopsies, the dominant IgG subtype remained unchanged over time.
  • A trend towards IgG1 and IgG3 (co)dominance was observed in biopsies taken >1 year post-recurrence and with advanced electron microscopy deposits; rituximab treatment did not alter IgG subtype.

Conclusions:

  • The dominant IgG subtype in immune deposits of recurrent membranous nephropathy (MN) generally does not change over time.
  • IgG4 is frequently the (co)dominant subtype at recurrence, regardless of PLA2R association.
  • Temporal stability of IgG subtypes suggests a persistent underlying pathogenic mechanism in recurrent MN.