title: A Proposal for a Serology-Based Approach to Membranous Nephropathy.
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.
authors: Division of Nephrology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium; an.devriese@azsintjan.be fervenza.fernando@mayo.edu.
authors: An S
authors: AS
authors: De Vriese
authors: Department of Medicine, Geffen School of Medicine, University of California, Los Angeles, California; and.
authors: Richard J
authors: RJ
authors: Glassock
authors: Division of Nephrology and Hypertension and.
authors: Karl A
authors: KA
authors: Nath
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors: Sanjeev
authors: S
authors: Sethi
authors: Division of Nephrology and Hypertension and an.devriese@azsintjan.be fervenza.fernando@mayo.edu.
authors: Fernando C
authors: FC
authors: Fervenza
mesh_terms: D000465:Algorithms; D001323:Autoantibodies / Q000097:blood; D015433:Glomerulonephritis, Membranous / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy; D006801:Humans; D016030:Kidney Transplantation; D011379:Prognosis; D054507:Receptors, Phospholipase A2 / Q000276:immunology; D012698:Serologic Tests
chemical_list: D001323:Autoantibodies; C516360:PLA2R1 protein, human; D054507:Receptors, Phospholipase A2
keywords: Immunology and pathology; PLA2R; THSD7A; clinical nephrology; membranous nephropathy