Zhang Liyin, Zhang Minfang, Xie Qionghong, Wang Yongxiang, Ni Zhaohui, Liu Shaojun, Zhou Wenyan
Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Nephrology, Molecular Cell Lab for Kidney Disease, Shanghai Peritoneal Dialysis Research Center, Uremia Diagnosis and Treatment Center, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kidney Int Rep. 2023 Nov 30;9(2):401-409. doi: 10.1016/j.ekir.2023.11.021. eCollection 2024 Feb.
Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown.
A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed.
Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection.
Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.
膜性肾病(MN)是梅毒中蛋白尿最常见的病因,最近有研究表明神经元源性神经营养因子(NDNF)是梅毒相关MN的靶抗原。然而,中国梅毒感染患者中NDNF阳性和NDNF阴性MN的患病率及临床病理特征仍不清楚。
对17例有梅毒感染史的MN患者进行回顾性研究。评估肾活检中NDNF染色的强度和分布,以及磷脂酶A2受体(PLA2R)和神经表皮生长因子样1蛋白(NELL-1)染色情况。
在11例有活动性梅毒感染的MN患者中,5例(46%)显示NDNF染色阳性。其余6例患者NDNF染色阴性。其中,5例患者PLA2R阳性,1例患者PLA2R阴性且NELL-1阴性。抗生素对3例NDNF阴性患者也有效,提示可能为梅毒相关MN。因此,梅毒相关MN中NDNF的组织学阳性率为63%(5/8例患者)。此外,首次在1例NDNF相关MN患者的血清中证实了NDNF抗体阳性。所有6例有既往梅毒感染史的MN患者NDNF染色均为阴性。
在我们的研究中,近一半有活动性梅毒感染和MN的患者NDNF呈阳性。NDNF染色阳性支持梅毒相关MN的诊断。可在患者血清样本中检测到循环抗NDNF抗体。此外,PLA2R或其他未知抗原蛋白也可能是中国人群中梅毒相关MN的靶抗原。