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EXT2 transition in adolescent membranous nephritis

Elizabeth Rackovan1, Gia Oh2, Sharon Su3

  • 1Department of Pathology and Laboratory Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code: L113, Portland, OR, 97239, USA.

Pediatric Nephrology (Berlin, Germany)
|December 5, 2025
PubMed

Insights

This case study highlights an adolescent with membranous nephropathy (MN) initially negative for common antigens. Later, EXT2-positive deposits appeared, indicating potential changes in MN antigen detection over time.

Area of Science:

  • Nephrology
  • Immunology
  • Pediatric Nephrology

Background:

  • Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in children, with rising incidence in adolescents.
  • Traditionally classified as primary or secondary, MN is now increasingly characterized by specific antigens.
  • Antigen identification in MN aids in understanding underlying conditions, prognosis, and treatment options.

Purpose of the Study:

  • To report a unique case of an adolescent with membranous nephropathy (MN).
  • To describe the diagnostic challenges and evolution of MN antigen detection.
  • To illustrate the potential for developing other kidney diseases, such as lupus nephritis, despite initial negative antigen status.

Main Methods:

  • Case report of an adolescent patient with nephrotic syndrome.
  • Kidney biopsy analysis for membranous nephropathy (MN) and associated antigens (PLA2R, NELL1, THSD7A, EXT2).
  • Monitoring of clinical presentation and treatment response, including B-cell depleting therapy and repeat biopsy.

Main Results:

  • The patient initially presented with MN negative for PLA2R, NELL1, THSD7A, and EXT2, responding to B-cell depletion.
  • Three years later, the patient developed proliferative lupus nephritis alongside ongoing membranous nephritis.
  • A subsequent kidney biopsy revealed newly detected EXT2-positive deposits, indicating a discordant antigen result over time.

Conclusions:

  • This case demonstrates that membranous nephropathy (MN) antigen detection can appear to change over time.
  • EXT1/2 negativity in initial MN biopsies does not preclude the later development of lupus nephritis in adolescents.
  • The findings underscore the complexity of MN diagnosis and the importance of longitudinal monitoring.
Keywords:
Exostosin 1/2LupusMembranous nephropathy

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