Retrospective analysis of serum NELL-1 and EXT1/2: no significant predictive value for treatment response in a cohort of membranous nephropathy patients

Neural epidermal growth factor-like protein 1 (NELL-1) and the exostosin 1/2 complex (EXT1/2) are recently identified target antigens in membranous nephropathy (MN), yet their prevalence and clinical features in Chinese populations remain poorly characterized. This study enrolled 197 consecutive patients with biopsy-proven MN, including 186 with idiopathic membranous nephropathy (IMN) and 11 with secondary membranous nephropathy (SMN). Serum levels of NELL-1 and EXT1/2 antigens were detected via enzyme-linked immunosorbent assay, with pre-biopsy baseline and at least one-year follow-up data collected for analysis. Among the participants, 152 were anti-phospholipase A2 receptor antibody-positive, while 8.6% (17/197) were positive for NELL-1 antigen and 6.5% (13/197) for EXT1/2 antigen. Following biopsy, 95.4% (188/197) of patients received treatment: 61.9% (122/188) underwent immunosuppressive therapy, and the remainder received RAAS-blockade alone. IgG subclass distributions varied significantly, with IgG4 predominating in 93.4% (142/152) of anti-PLA2R antibody-positive cases, whereas IgG1 was dominant in 58.9% (10/17) of NELL-1 antigen-positive and 84.6% (11/13) of EXT1/2 antigen-positive cases. After a median follow-up of 13.0 months, 67.5% (133/197) achieved proteinuria remission. In conclusion, NELL-1 and EXT1/2 antigens were detected in 8.63% and 6.60% of patients, respectively; however, antigen status did not predict treatment response or clinical outcomes such as proteinuria remission.