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Optimization of a Target Antigen Diagnostic Pathway for Membranous Nephropathy
Wangyang Li1, Cheng Huang2, Shuling Yue3
1Department of Nephrology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
Introduction:
The recent Mayo Clinic consensus proposed a target antigen-based diagnostic pathway for membranous nephropathy (MN), recommending testing for neural epidermal growth factor-like 1 (NELL1) following a negative phospholipase A2 receptor (PLA2R) result. This study aimed to optimize this pathway in a real-world Chinese cohort enriched for diagnostic complexity.
Methods:
This dual-center retrospective study included 816 patients with PLA2R staining on renal biopsy (2008-2023). PLA2R-negative patients with atypical features and available tissue underwent comprehensive testing for thrombospondin type-1 domain-containing 7A (THSD7A), NELL1, exostosin1/2 (EXT1/2), semaphorin 3B (SEMA3B), and protocadherin 7 (PCDH7). Testing efficiency was simulated in a subcohort comprising all PLA2R-positive patients and PLA2R-negative patients with complete antigen data.
Results:
PLA2R positivity was 73.90%. Among PLA2R-negative patients (n = 159 with complete data), EXT1/2 (9.43%), and NELL1 (7.55%) were the most prevalent non-PLA2R antigens, with near-complete mutual exclusivity. Two sequential strategies (Mayo order vs. our cohort-derived order) achieved identical final cumulative diagnostic yield (83.33%). Most 7-antigen-negative patients (64.29%) had secondary MN, predominantly lupus nephritis (LN).
Conclusion:
In Chinese PLA2R-negative patients with atypical features, EXT1/2 and NELL1 are the predominant antigens. Sequential testing by local prevalence (PLA2R → EXT1/2 → NELL1) is resource-efficient, whereas concurrent testing offers time savings. This practical framework aids diagnostic optimization, especially for patients with an autoimmune phenotype.
