Abstract
The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Evaluation of serum levels of anti-podocyte antibodies paved the way for non-invasive diagnosis and helped distinguish between primary and secondary MN although the relationship between anti-podocyte antibodies and cancer remains to be elucidated. Serum levels of anti-PLA2R antibodies directed against the major podocyte autoantigen are related to MN activity and the decrease in serum levels of anti-PLA2R antibodies in response to treatment (immunologic remission) also serves as an early indicator of the later putative proteinuric remission, enabling personalization of the treatment. The serum levels of anti-podocyte antibodies also enable the prediction of renal outcomes in terms of both remission and the risk of progression to end-stage renal disease. The positivity of anti-PLA2R antibodies before renal transplantation is associated with the risk of recurrence of MN. It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are also valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B).
Highlights
The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease
It remains to be established if all these relations observed in patients with anti-PLA2R antibodies are valid for expanding spectrum of antibodies directed against recently discovered minor antigens (e.g., THSD7A, NELL-1, semaphorin 3B)
As anti-podocyte antibodies are highly specific for primary MN [well-documented for anti-PLA2R antibodies, where the specificity is 98–100% [54]] it has been suggested that the diagnosis of primary MN may be assessed in patients with nephrotic syndrome, normal renal function and positive antiPLA2R antibodies even without renal biopsy [54]
Summary
The discovery of anti-podocyte antibodies in primary membranous nephropathy (MN) has revolutionized our approach toward the diagnosis and treatment of this disease. Glomerular binding of anti-PLA2R antibodies is highly specific for primary MN, it occurs in some patients with HBV, sarcoidosis, or cancer-associated secondary membranous nephropathies. In some patients with MN positive for glomerular PLA2R staining, circulating antibodies may not be detectable at presentation, but may occur later during follow-up (and treatment) of the disease [36].
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