Neural Epidermal Growth Factor-Like 1 Protein-Positive Membranous Nephropathy in Chinese Patients.
BACKGROUND AND OBJECTIVES
The neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1-positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear.


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened. Glomerular immunohistochemistry staining for NELL-1 was performed in 43 patients with PLA2R- and THSD7A-negative membranous nephropathy, 31 patients with PLA2R-positive membranous nephropathy, and two patients with PLA2R and THSD7A double positivity. The NELL-1 antibody was also detected in the sera of patients with NELL-1-positive membranous nephropathy by western blot. Clinical and pathologic features were comparable between patients with isolated NELL-1-positive, isolated PLA2R/THSD7A-positive, and triple antigen-negative membranous nephropathy.


RESULTS
Among the 832 patients with primary membranous nephropathy, 11 of 54 (20%) patients with PLA2R-negative membranous nephropathy had THSD7A-positive membranous nephropathy. NELL-1-positive membranous nephropathy accounted for 35% (15 of 43) of all patients with PLA2R- and THSD7A-negative membranous nephropathy. One patient was double positive for NELL-1 and PLA2R in glomerular deposits and positive for only the PLA2R antibody in the serum. Most patients with NELL-1-positive membranous nephropathy were women. No tumors were found. There were significant differences in the prevalence of IgG subtypes between patients with different antigen positivity. Among patients with isolated NELL-1-positive membranous nephropathy, although 80% (12 of 15) were IgG4 staining positive, the proportion of IgG4 dominance was only 67% (ten of 15).


CONCLUSIONS
About one third of patients who were PLA2R and THSD7A negative were NELL-1 positive in Chinese patients with primary membranous nephropathy. NELL-1-positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.
['Wang|Guoqin|G|', 'Sun|Lijun|L|', 'Dong|Hongrui|H|', 'Wang|Yanyan|Y|', 'Xu|Xiaoyi|X|', 'Zhao|Zhirui|Z|', 'Cheng|Wenrong|W|', 'Liu|Xuejiao|X|', 'Zhao|Xiaoyi|X|', 'Geng|Yanqiu|Y|', 'Bao|Siqin|S|', 'Chen|Yipu|Y|', 'Cheng|Hong|H|0000-0002-7908-3333']
membranous nephropathy neural epidermal growth factor-like 1 protein phospholipaseA2 receptor thrombospondintype 1 domain-containing7A