A case of syphilis-associated membranous nephropathy with NDNF detected by immunohistochemistry, not by mass spectrometry: case report and literature review

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.