VEGF-A Links Angiolymphoid Hyperplasia With Eosinophilia (ALHE) to THSD7A Membranous Nephropathy: A Report of 2 Cases.

Autoantibodies against thrombospondin type 1 domain-containing 7A (THSD7A) cause membranous nephropathy (MN); however, the mechanisms involved in THSD7A expression and immunization are uncertain. We present 2 cases of THSD7A-associated MN accompanied by angiolymphoid hyperplasia with eosinophilia (ALHE), a benign tumor characterized by proliferation of plump endothelial cells. Prednisolone therapy, but not surgical resection of ALHE tumors, successfully suppressed eosinophilia and proteinuria in both cases. Because ALHE is characterized by the proliferation of plump endothelial cells, we focused on the roles of vascular endothelial growth factor A (VEGF-A) in MN pathogenesis. We found that plump endothelial cells in ALHE modestly expressed THSD7A in both cases. We also found that eosinophils in ALHE expressed VEGF-A, which upregulated THSD7A expression, especially under T-helper type 2-prone conditions in cultured endothelial cells. Furthermore, double-positive cells for THSD7A and CD83 surrounded the proliferated small vessels. Our results suggest that VEGF-A-induced THSD7A expression outside the kidney may be important for MN pathogenesis. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Citation

Ayumi Matsumoto, Isao Matsui, Tomoko Namba, Yusuke Sakaguchi, Hitoshi Mizuno, Yuki Shirayama, Karin Shimada, Nobuhiro Hashimoto, Yohei Doi, Satoshi Yamaguchi, Keiichi Kubota, Tatsufumi Oka, Daisuke Mori, Shinichi Akiyama, Takayuki Hamano, Masayuki Mizui, Yoshitsugu Takabatake, Tetsuya Kaneko, Yoshitaka Isaka. VEGF-A Links Angiolymphoid Hyperplasia With Eosinophilia (ALHE) to THSD7A Membranous Nephropathy: A Report of 2 Cases. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2019 Jun;73(6):880-885

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PMID: 30554801

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