Exostosin 1/Exostosin 2-Associated Membranous Nephropathy

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Membranous nephropathy (MN) involves immune complex deposition on the glomerular basement membrane (GBM).
• Phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A are known antigens in primary MN, but targets remain unknown in other cases.
• Identifying novel antigens is crucial for understanding and diagnosing MN subtypes.

Purpose of the Study:

• To identify novel target antigens in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN).
• To investigate the association of newly identified antigens with autoimmune diseases.

Main Methods:

• Analysis of 224 biopsy-proven PLA2R-negative MN cases and 102 controls.
• Utilized laser microdissection and mass spectrometry to detect novel antigens.
• Immunohistochemistry was employed to localize identified antigens.

Main Results:

• Exostosin 1 (EXT1) and exostosin 2 (EXT2) were detected in 21 cases of PLA2R-negative MN.
• Immunohistochemistry confirmed granular GBM staining for EXT1 and EXT2.
• 80.7% of EXT1/EXT2-associated MN cases exhibited features of autoimmune disease, including lupus nephritis.

Conclusions:

• A subset of MN is characterized by the accumulation of EXT1 and EXT2 in the GBM.
• Autoimmune diseases are frequently observed in patients with EXT1/EXT2-associated MN.
• These findings expand the known antigenic targets in MN and highlight its association with systemic autoimmunity.