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Target Antigens of Membranous Nephropathy With Syphilis Infection
Liyin Zhang1, Minfang Zhang2, Qionghong Xie1
1Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Neuron-derived neurotrophic factor (NDNF) is a target antigen in syphilis-associated membranous nephropathy (MN). Nearly half of active syphilis patients with MN showed positive NDNF staining, suggesting its role in this condition.
Area of Science:
- Nephrology
- Immunology
- Infectious Diseases
Background:
- Membranous nephropathy (MN) is a leading cause of proteinuria in syphilis.
- Neuron-derived neurotrophic factor (NDNF) has been identified as a target antigen in syphilis-associated MN.
- The prevalence and characteristics of NDNF-positive and negative MN in Chinese syphilis patients were previously unknown.
Purpose of the Study:
- To investigate the prevalence and clinicopathological features of NDNF-positive and NDNF-negative MN in Chinese patients with syphilis infection.
- To assess the diagnostic role of NDNF staining and circulating anti-NDNF antibodies in syphilis-associated MN.
Main Methods:
- Retrospective analysis of 17 patients with MN and a history of syphilis infection.
- Assessment of NDNF, phospholipase A2 receptor (PLA2R), and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies.
- Serum anti-NDNF antibody detection.
Main Results:
- Among 11 patients with active syphilis and MN, 5 (46%) exhibited positive NDNF staining.
- The histological positivity rate of NDNF was 63% in syphilis-associated MN (5/8 patients).
- Positive NDNF staining was absent in patients with previous syphilis infection; circulating anti-NDNF antibody was detected in one patient.
Conclusions:
- Nearly half of active syphilis-associated MN cases in this cohort were NDNF-positive.
- Positive NDNF staining supports syphilis as the cause of MN.
- PLA2R or other antigens may also be involved in syphilis-associated MN in the Chinese population.

