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New antigens involved in membranous nephropathy beyond phospholipase A2 receptor
Maurizio Salvadori1, Aris Tsalouchos2
1Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Tuscany, Italy. maurizio.salvadori1@gmail.com.
Abstract:
When the physiopathology of membranous nephropathy was first described, almost 30% of cases were recognized to be secondary to well-known diseases such as autoimmune diseases, tumors or infections. The remaining 70% cases were called primary membranous nephropathy as the exact mechanism or pathogenic factor involved was unknown. The discovery of the M type phospholipase A2 receptor and thrombospondin type 1 domain containing 7A as causative antigens in these "so called" primary membranous nephropathies provided new insights into the effective causes of a large proportion of these cases. Novel techniques such as laser microdissection and tandem mass spectrometry as well as immunochemistry with antibodies directed against novel proteins allowed the confirmation of new involved antigens. Finally, using confocal microscopy to localize these new antigens and immunoglobulin G and Western blot analysis of serum samples, these new antigens were detected on the glomerular membrane, and the related antibodies were detected in serum samples. The same antigens have been recognized in some cases of secondary membranous disease due to autoimmune diseases, tumors and infections. This has allowed examination of the relationship between antigens in primary membranous nephropathy and their presence in some secondary nephropathies. The aim of this study is to describe the characteristics of the new antigens discovered and their association with other diseases.
Insights
New research identifies key antigens, like the phospholipase A2 receptor, involved in primary membranous nephropathy. These discoveries also link to secondary causes, improving understanding of this kidney disease.
Area of Science:
- Nephrology
- Immunology
- Pathophysiology
Background:
- Membranous nephropathy (MN) is often idiopathic, with 70% classified as primary MN due to unknown pathogenic factors.
- Previously, only a few causes were known for secondary MN, including autoimmune diseases, infections, and tumors.
Purpose of the Study:
- To characterize newly discovered antigens implicated in primary membranous nephropathy.
- To investigate the association of these antigens with secondary forms of membranous nephropathy.
Main Methods:
- Utilized laser microdissection and tandem mass spectrometry to identify novel antigens.
- Employed immunochemistry, confocal microscopy, and Western blot analysis to detect antigens and antibodies.
Main Results:
- Identified phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) as major antigens in primary MN.
- Confirmed the presence of these antigens and their corresponding antibodies in glomerular membranes and serum samples.
- Observed overlap of these antigens in some cases of secondary MN linked to autoimmune diseases, tumors, and infections.
Conclusions:
- The discovery of PLA2R and THSD7A has significantly advanced the understanding of primary MN's etiology.
- These findings establish a link between antigens in primary MN and their presence in certain secondary MN cases.
- This research provides new diagnostic and potentially therapeutic insights into membranous nephropathy.
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