Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Primary membranous nephropathy (MN) involves autoantibodies targeting podocyte surface antigens.
• Phospholipase A2 receptor 1 (PLA2R1) is the primary antigen in most MN cases, but some cases remain unexplained.

Purpose of the Study:

• To identify novel autoantibody targets in patients with primary membranous nephropathy (MN) where the cause is unknown.
• To investigate the role of Netrin G1 (NTNG1) as a potential antigen in MN pathogenesis.

Main Methods:

• Native western blotting and mass spectrometry were used to identify target antigens from patient serum.
• ELISA and immunohistochemistry were employed to analyze NTNG1 autoantibodies and expression in patient cohorts.
• Patient cohorts included 888 individuals with MN and other glomerular diseases.

Main Results:

• Netrin G1 (NTNG1) was identified as a novel target antigen in MN, expressed on podocyte membranes.
• Three patients with MN exhibited IgG4-dominant NTNG1 autoantibodies, increased kidney NTNG1 expression, and glomerular IgG4 deposits.
• NTNG1 autoantibodies were not found in patients with PLA2R1 or THSD7A antibodies, or other glomerular diseases.

Conclusions:

• Netrin G1 (NTNG1) represents a newly discovered target antigen in primary membranous nephropathy (MN).
• The findings expand the known antigenic targets in MN, offering potential for improved diagnostics.
• Further research is needed to define the precise clinical significance of NTNG1 autoantibodies in MN.