Sakamoto Emi, Shimada Keiki, Takeuchi Kazuhiro, Kuno Hideaki, Yamada Haruka, Suzuki Minami, Katagiri Daisuke, Shimizu Akira, Takano Hideki
Department of Nephrology, Japan Institute for Health Security, National Center for Global Health and Medicine, Nephrology, 1-21-1, Toyama, Shinjuku, Tokyo, 168-8655, Japan.
Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
CEN Case Rep. 2025 May 14. doi: 10.1007/s13730-025-00997-0.
Syphilis is an infectious disease caused by the spirochete Treponema pallidum and is increasingly prevalent worldwide, with a rapid increase in reported cases in Japan in recent years. Syphilis is characterized by skin lesions, lymphadenopathy, and hepatosplenomegaly but is rarely manifested by renal disorders, including membranous nephropathy (MN). Neuron-derived neurotrophic factor (NDNF) is an antigen specific for syphilis-associated MN. This report describes a case of NDNF-related MN after syphilis infection in a 42-year-old male who developed nephrotic syndrome 3 months after infection. Renal biopsy under light microscopy revealed mild mesangial proliferation without spike formation in the glomerular basement membrane. Immunofluorescence and electron microscopy revealed granular deposits of IgM, IgG, C1q, and C3 on the capillary walls, with subepithelial hump-like electron-dense deposits (EDDs), consistent with stage I MN. Immunohistochemistry confirmed the presence of NDNF. In contrast, other common antigens related to primary MN, such as M-type phospholipase A2 receptor and thrombospondin type I domain-containing 7A, were negative on mass spectrometry. The patient achieved remission with antibiotic therapy alone. This case and the literature review on NDNF-related MN highlight the relevance of NDNF as a syphilis-associated MN antigen and demonstrate that antibiotic therapy alone without immunosuppressive drugs can lead to remission. Mass spectrometry can accurately identify MN antigens; however, immunostaining is more effective in cases where EDDs are segmental and antigen concentration is low. Our findings indicate that NDNF testing should be performed in cases of proteinuria associated with syphilis to help guide antibiotic therapy and reduce immunosuppression.
梅毒是一种由梅毒螺旋体引起的传染病，在全球范围内日益流行，近年来日本报告的病例迅速增加。梅毒的特征是皮肤病变、淋巴结病和肝脾肿大，但很少表现为肾脏疾病，包括膜性肾病（MN）。神经元源性神经营养因子（NDNF）是梅毒相关MN的特异性抗原。本报告描述了一例42岁男性梅毒感染后发生NDNF相关MN的病例，该患者在感染后3个月出现肾病综合征。光镜下肾活检显示轻度系膜增生，肾小球基底膜无钉突形成。免疫荧光和电子显微镜检查显示毛细血管壁有IgM、IgG、C1q和C3的颗粒状沉积，伴有上皮下驼峰样电子致密沉积物（EDD），符合I期MN。免疫组化证实存在NDNF。相比之下，与原发性MN相关的其他常见抗原，如M型磷脂酶A2受体和含血小板反应蛋白I型结构域的7A，质谱检测为阴性。该患者仅通过抗生素治疗就实现了缓解。该病例及关于NDNF相关MN的文献综述强调了NDNF作为梅毒相关MN抗原的相关性，并表明仅用抗生素治疗而不使用免疫抑制药物可导致缓解。质谱可准确识别MN抗原；然而，在EDD呈节段性且抗原浓度较低的情况下，免疫染色更有效。我们的研究结果表明，对于与梅毒相关的蛋白尿病例，应进行NDNF检测，以帮助指导抗生素治疗并减少免疫抑制。
