Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, China.
Clin J Am Soc Nephrol. 2021 May 8;16(5):727-735. doi: 10.2215/CJN.11860720. Epub 2021 Apr 13.
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.
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).
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.
神经表皮生长因子样 1（NELL-1）蛋白是原发性膜性肾病的一种新型抗原。在中国原发性膜性肾病患者中，NELL-1 阳性膜性肾病的患病率和临床特征尚不清楚。
设计、地点、参与者和测量方法：共纳入 832 例经活检证实的原发性膜性肾病患者。筛选磷脂酶 A2 受体（PLA2R）和血小板反应蛋白 1 型域包含 7A（THSD7A）在肾小球中的表达。对 PLA2R 和 THSD7A 阴性膜性肾病的 43 例、PLA2R 阳性膜性肾病的 31 例和 PLA2R 和 THSD7A 双重阳性的 2 例患者进行肾小球免疫组织化学染色以检测 NELL-1。通过 Western blot 检测 NELL-1 阳性膜性肾病患者血清中的 NELL-1 抗体。孤立的 NELL-1 阳性、孤立的 PLA2R/THSD7A 阳性和三抗原阴性膜性肾病患者的临床和病理特征具有可比性。
在 832 例原发性膜性肾病患者中，54 例 PLA2R 阴性膜性肾病患者中有 11 例为 THSD7A 阳性膜性肾病。NELL-1 阳性膜性肾病占所有 PLA2R 和 THSD7A 阴性膜性肾病患者的 35%（43 例中的 15 例）。1 例患者肾小球沉积物中同时存在 NELL-1 和 PLA2R 阳性，血清中仅 PLA2R 抗体阳性。大多数 NELL-1 阳性膜性肾病患者为女性。未发现肿瘤。不同抗原阳性患者 IgG 亚型的患病率存在显著差异。在孤立的 NELL-1 阳性膜性肾病患者中，尽管 80%（15 例中的 12 例）为 IgG4 染色阳性，但 IgG4 优势的比例仅为 67%（15 例中的 10 例）。
在中国原发性膜性肾病患者中，约三分之一的 PLA2R 和 THSD7A 阴性患者为 NELL-1 阳性。在 PLA2R 阴性膜性肾病患者中，NELL-1 阳性膜性肾病比 THSD7A 阳性膜性肾病更为常见。
