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M-type Phospholipase A2 Receptor (PLA2R) and Thrombospondin Type-1 Domain-Containing 7A (THSD7A) in Membranous Nephropathy

  • Chapter
Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome

Abstract

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in Caucasians adults. It is defined by the presence of subepithelial immune deposits localized between the podocyte and the glomerular basement membrane (GBM) on electron microscopy examination (EM). Clinical course is variable: although up to 30 % of patients may go into spontaneous remission, approximately 40 % of patients eventually develop ESRD. The discovery of two major podocytes antigens in adults: first, the M-type phospholipase A2 receptor 1 (PLA2R1) and more recently, the thrombospondin type-1 domain-containing 7A (THSD7A) protein has revolutionized our understanding of the pathogenesis of human MN. Approximately 75 % of patients with active disease have circulating anti-PLA2R autoantibodies, and up to 10 % of the patients with MN that are anti-PLA2R negative have antibodies against THSD7A. Quantification and follow-up of anti-PLA2R levels have major implications regarding prognosis and treatment response. The presence of anti-PLA2R antibodies can also predict disease recurrence following kidney transplantation. Genetic studies are elucidating predisposing factors for development of the disease. Further research into the antigen-autoantibody systems is likely to elucidate a clearer understanding of the pathophysiology and treatment of patients with MN.

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Authors and Affiliations

  1. Renal Section, Boston University School of Medicine, Boston, MA, USA

    Laurence H. Beck M.D., Ph.D.

  2. Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA

    Sanjeev Sethi M.D., Ph.D.

  3. Division of Nephrology and Hypertension, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA

    Fernando C. Fervenza M.D., D.Phil.

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  1. Laurence H. Beck M.D., Ph.D.
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  2. Sanjeev Sethi M.D., Ph.D.
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  3. Fernando C. Fervenza M.D., D.Phil.
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Correspondence to Fernando C. Fervenza M.D., D.Phil. .

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  1. Department of Pediatrics, Kansai Medical University, Hirakata, Osaka, Osaka, Japan

    Kazunari Kaneko

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Beck, L.H., Sethi, S., Fervenza, F.C. (2016). M-type Phospholipase A2 Receptor (PLA2R) and Thrombospondin Type-1 Domain-Containing 7A (THSD7A) in Membranous Nephropathy. In: Kaneko, K. (eds) Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55270-3_11

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