Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Am J Kidney Dis. 2019 Jun;73(6):880-885. doi: 10.1053/j.ajkd.2018.10.009. Epub 2018 Dec 13.
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.
自身抗体针对血栓反应蛋白 1 型结构域包含 7A 型（THSD7A）可导致膜性肾病（MN）；然而，THSD7A 表达和免疫的机制尚不确定。我们报告了 2 例伴有血管淋巴样增生伴嗜酸性粒细胞增多症（ALHE）的 THSD7A 相关 MN，ALHE 是一种良性肿瘤，其特征是丰满的内皮细胞增殖。泼尼松龙治疗，而不是手术切除 ALHE 肿瘤，成功地抑制了两例中的嗜酸性粒细胞增多和蛋白尿。由于 ALHE 的特征是丰满的内皮细胞增殖，我们专注于血管内皮生长因子 A（VEGF-A）在 MN 发病机制中的作用。我们发现，在两种情况下，ALHE 中的丰满内皮细胞适度表达 THSD7A。我们还发现，ALHE 中的嗜酸性粒细胞表达 VEGF-A，这在上皮细胞培养中尤其在辅助性 T 细胞 2 倾向条件下上调了 THSD7A 的表达。此外，THSD7A 和 CD83 双阳性细胞环绕增殖的小血管。我们的结果表明，VEGF-A 诱导的肾外 THSD7A 表达可能对 MN 发病机制很重要。
