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

A Proposal for a Serology-Based Approach to Membranous Nephropathy.

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Division of Nephrology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium;
Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, California; and.
Division of Nephrology and Hypertension and.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Division of Nephrology and Hypertension and


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.


Immunology and pathology; PLA2R; THSD7A; clinical nephrology; membranous nephropathy

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