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抗 DFS70 抗体输注延长狼疮易感小鼠的生存时间。

Infusion of anti-DFS70 antibodies prolonged survival of lupus-prone mice.

机构信息

Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Israel.

Rheumatology Division, Department of Medicine, Escola Paulista de Medicina, University Federal Sao Paulo, Sao Paulo, Brazil.

出版信息

Lupus. 2021 Feb;30(2):320-324. doi: 10.1177/0961203320969976. Epub 2020 Nov 11.

DOI:10.1177/0961203320969976
PMID:33175665
Abstract

BACKGROUND

Systemic-lupus-nephritis is a chronic autoimmune disease characterized by immune complex deposition and a flare of autoantibodies and leading to renal injury.

OBJECTIVES

To expose anti-Dense-Fine-Speckled-70 (DFS70)-antibodies to genetically-prone-lupus-mice.

METHODS

NZBXW/F1 female mice were monitored for the onset of glomerulonephritis by proteinuria upon infusion of anti-DFS70 (40 μg/mouse), commercial-human-IgG (cIgG) or phosphate-buffered-saline (PBS) as controls. The survival time was detected by mice death. Circulating anti-dsDNA were tested by ELISA. Proteinuria, was defined by a standard semi-quantitative-Bayer-Multistix-dipstick. Kidney histology was analyzed by periodic-acid-Schiff-PAS staining.

RESULTS

A significantly higher percentage of anti-DFS70-infused mice exhibited prolonged survival time as compared with cIgG and PBS-subjected mice (p < 0.022). One mouse out of 10 mice injected with anti-DFS70-antibodies died at week 36, whereas, 6 out of 10 mice subjected with PBS found dead at this time. Eighty percent of anti-DFS70 injected mice did not show severe glomerulonephritis by histology.

CONCLUSIONS

anti-DFS70 attenuated the progression of glomerulonephritis and prolonged the survival time. Circulating anti-DFS70-autoantibodies may confer a protective role against renal injury in murine-lupus-nephritis. Our data may propose a novel therapy approach for lupus patients.

摘要

背景

系统性红斑狼疮是一种慢性自身免疫性疾病,其特征是免疫复合物沉积和自身抗体爆发,导致肾脏损伤。

目的

向遗传易患狼疮的小鼠暴露抗致密细斑点 70(DFS70)抗体。

方法

通过蛋白尿监测 NZBXW/F1 雌性小鼠在输注抗 DFS70(40μg/只)、商业人 IgG(cIgG)或磷酸盐缓冲盐水(PBS)作为对照时肾小球肾炎的发病情况。通过小鼠死亡检测存活时间。通过 ELISA 检测循环抗 dsDNA。蛋白尿通过标准半定量 Bayer Multistix 尿试纸条定义。通过过碘酸希夫 PAS 染色分析肾脏组织学。

结果

与 cIgG 和 PBS 处理的小鼠相比,接受抗 DFS70 抗体输注的小鼠的存活率明显更高(p<0.022)。10 只接受抗 DFS70 抗体注射的小鼠中有 1 只在第 36 周死亡,而此时接受 PBS 的 10 只小鼠中有 6 只死亡。80%接受抗 DFS70 抗体注射的小鼠在组织学上没有出现严重的肾小球肾炎。

结论

抗 DFS70 可减轻肾小球肾炎的进展并延长存活时间。循环抗 DFS70 自身抗体可能在狼疮性肾炎的小鼠中发挥保护作用。我们的数据可能为狼疮患者提出一种新的治疗方法。

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