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A Proposal for a Serology-Based Approach to Membranous Nephropathy

An S. De Vriese, Richard J. Glassock, Karl A. Nath, Sanjeev Sethi and Fernando C. Fervenza
JASN February 2017, 28 (2) 421-430; DOI: https://doi.org/10.1681/ASN.2016070776
An S. De Vriese
*Division of Nephrology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium;
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Richard J. Glassock
†Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, California; and
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Karl A. Nath
‡Division of Nephrology and Hypertension and
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Sanjeev Sethi
§Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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Fernando C. Fervenza
‡Division of Nephrology and Hypertension and
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Abstract

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.

  • membranous nephropathy
  • clinical nephrology
  • Immunology and pathology
  • PLA2R
  • THSD7A
  • Copyright © 2017 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 28 (2)
Journal of the American Society of Nephrology
Vol. 28, Issue 2
February 2017
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A Proposal for a Serology-Based Approach to Membranous Nephropathy
An S. De Vriese, Richard J. Glassock, Karl A. Nath, Sanjeev Sethi, Fernando C. Fervenza
JASN Feb 2017, 28 (2) 421-430; DOI: 10.1681/ASN.2016070776

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A Proposal for a Serology-Based Approach to Membranous Nephropathy
An S. De Vriese, Richard J. Glassock, Karl A. Nath, Sanjeev Sethi, Fernando C. Fervenza
JASN Feb 2017, 28 (2) 421-430; DOI: 10.1681/ASN.2016070776
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  • Article
    • Abstract
    • Autoantibody Assays and Antigen Staining
    • Serology-Based Diagnosis
    • Serology-Based Assessment of Prognosis
    • Serology-Based Monitoring of Treatment
    • Serology-Based Monitoring of Post-Transplant Recurrence
    • Conclusion
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Keywords

  • membranous nephropathy
  • clinical nephrology
  • immunology and pathology
  • PLA2R
  • THSD7A

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