Abstract: TH-PO199
Possible Contribution of Vascular Endothelial Growth Factor A (VEGF-A) to the Pathogenesis of Membranous Nephropathy (MN)
Session Information
- Fellows/Residents Case Reports: Glomerulonephritis
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Nephrology Education
- 1302 Fellows and Residents Case Reports
Authors
- Matsumoto, Ayumi, Osaka University Graduate School of Medicine, Suita, Japan
- Matsui, Isao, Osaka University Graduate School of Medicine, Suita, Japan
- Namba, Tomoko, Osaka University Graduate School of Medicine, Suita, Japan
- Sakaguchi, Yusuke, Osaka University Graduate School of Medicine, Suita, Japan
- Mizui, Masayuki, Osaka University Graduate School of Medicine, Suita, Japan
- Hamano, Takayuki, Osaka University Graduate School of Medicine, Suita, Japan
- Isaka, Yoshitaka, Osaka University Graduate School of Medicine, Suita, Japan
Background
Autoantibody against thrombospondin type-1 domain-containing 7A (THSD7A) is responsible for primary MN, but the mechanisms how is THSD7A-expression controlled and how is THSD7A recognized by the immune system remain uncertain.
Methods
Two cases of THSD7A-associated MN accompanying subcutaneous tumors were transferred to our hospital. Hypereosinophilia was evident in both cases. Histological analyses of forehead tumors of Case 1 revealed that the tumors were formed by swollen arteries. The arteries were nearly occluded due to small vessels lined by CD31-positive plump endothelial cells, which were surrounded by eosinophils. These findings indicated that the patient suffered from intra-arterial angiolymphoid hyperplasia with eosinophilia (ALHE). The right axillary tumor of Case 2 indicated that Case 2 also suffered from ALHE. Plasma VEGF-A before the initiation of prednisolone therapy was elevated to 109 pg/mL in Case 1 (normal level: 42 ± 20 pg/mL). Serum level of IL-5, a cytokine that upregulates VEGF-A production and secretion by eosinophils, was also elevated to 15.5 pg/mL in Case 1 (normal level: <3.9 pg/mL). These parameters were not measured in Case 2. Flow cytometric analysis of peripheral blood revealed that a substantial number of the circulating eosinophils was positive for VEGF-A in Case 1, and eosinophils infiltrated into the ALHE tumor were also positive for VEGF-A in both cases. Prednisolone therapy dramatically decreased the number of VEGF-positive eosinophils and plasma VEGF-A levels (57.3 pg/mL). We found that plump endothelial cells in ALHE strongly expressed THSD7A in both cases. VEGF-A upregulated THSD7A expression in a dose-dependent manner in cultured human umbilical-vein endothelial cells. Furthermore, double-positive cells for THSD7A and CD83, a molecule involved in antigen-presentation activity, surrounded the proliferated small vessels. These findings suggested that VEGF-A-induced THSD7A was presented to the immune system at ALHE foci.
Conclusion
Our study clearly demonstrated that VEGF-A induced THSD7A expression. The existence of THSD7A/CD83 double-positive cells in ALHE tumors suggested that THSD7A was immunized at ALHE foci. Therefore, VEGF-A-induced THSD7A-expression outside of the kidney plays important roles in MN pathogenesis.
Funding
- Private Foundation Support