Lupus Nephritis Patterns and Response to Type I Interferon in Patients With DNASE1L3 Variants: Report of Three Cases.

IF 9.4 1区 医学 Q1 UROLOGY & NEPHROLOGY
American Journal of Kidney Diseases Pub Date : 2024-12-01 Epub Date: 2024-07-24 DOI:10.1053/j.ajkd.2024.05.014
Stefano Volpi, Maria L Angelotti, Giulia Palazzini, Giulia Antonelli, Fiammetta Ravaglia, Federica Garibotto, Anna Agrusti, Alice Grossi, Alberto Magnasco, Giovanni M Rossi, Carmela Errichiello, Francesco Peyronel, Elisa Buti, Lorenzo Lodi, Gian M Ghiggeri, Paola Romagnani, Augusto Vaglio
{"title":"Lupus Nephritis Patterns and Response to Type I Interferon in Patients With DNASE1L3 Variants: Report of Three Cases.","authors":"Stefano Volpi, Maria L Angelotti, Giulia Palazzini, Giulia Antonelli, Fiammetta Ravaglia, Federica Garibotto, Anna Agrusti, Alice Grossi, Alberto Magnasco, Giovanni M Rossi, Carmela Errichiello, Francesco Peyronel, Elisa Buti, Lorenzo Lodi, Gian M Ghiggeri, Paola Romagnani, Augusto Vaglio","doi":"10.1053/j.ajkd.2024.05.014","DOIUrl":null,"url":null,"abstract":"<p><p>DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 variants impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 variants is poorly characterized. Herein, we describe the clinical course of 3 children with monogenic SLE due to DNASE1L3 variants who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (ie, membranous, endocapillary, and extracapillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN-I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. Two of the patients had increased expression of interferon-stimulated genes in the peripheral blood, and all 3 patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN-I-mediated kidney disorders and provide the rationale for IFN-I-directed therapies in order to improve the poor outcome of this rare condition.</p>","PeriodicalId":7419,"journal":{"name":"American Journal of Kidney Diseases","volume":" ","pages":"791-797"},"PeriodicalIF":9.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Kidney Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1053/j.ajkd.2024.05.014","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/24 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

DNASE1L3 is an extracellular nuclease that digests chromatin released from apoptotic cells. DNASE1L3 variants impair the enzyme function, enhance autoantibody production and type I interferon (IFN-I) responses, and cause different autosomal recessive phenotypes ranging from hypocomplementemic urticarial vasculitis syndrome to full-blown systemic lupus erythematosus (SLE). Kidney involvement in patients with DNASE1L3 variants is poorly characterized. Herein, we describe the clinical course of 3 children with monogenic SLE due to DNASE1L3 variants who developed refractory glomerulonephritis leading to kidney failure. They had different renal histopathological patterns (ie, membranous, endocapillary, and extracapillary glomerulonephritis and thrombotic microangiopathy), all belonging to the lupus nephritis (LN) spectrum. One patient had a mixed phenotype, showing an overlap between SLE and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Using immunofluorescence, we detected glomerular expression of the IFN-I-induced human myxovirus resistance protein 1 (MXA), which was particularly evident in glomerular endothelial cells. Two of the patients had increased expression of interferon-stimulated genes in the peripheral blood, and all 3 patients had reduced serum DNAse activity. Our findings suggest that DNASE1L3-related glomerulonephritis can be included in the spectrum of IFN-I-mediated kidney disorders and provide the rationale for IFN-I-directed therapies in order to improve the poor outcome of this rare condition.

DNASE1L3突变患者的狼疮肾炎模式和对I型干扰素的反应:三个病例的报告
DNASE1L3 是一种细胞外核酸酶,可消化凋亡细胞释放的染色质。DNASE1L3 基因突变会损害酶的功能,增强自身抗体的产生和 I 型干扰素(IFN-I)的反应,并导致不同的常染色体隐性遗传表型,从低补体荨麻疹性血管炎综合征到全面的系统性红斑狼疮(SLE)。DNASE1L3基因突变患者的肾脏受累情况尚不明确。在此,我们描述了三名因 DNASE1L3 基因突变而患单基因系统性红斑狼疮的儿童的临床病程,他们患上了难治性肾小球肾炎,导致肾衰竭。他们的肾脏组织病理形态各异(即膜性、毛细血管内和毛细血管外肾小球肾炎以及血栓性微血管病),均属于狼疮肾炎(LN)谱系。一名患者的表型为混合型,显示出系统性红斑狼疮和ANCA相关性血管炎的重叠。通过免疫荧光技术,我们检测到了 IFN I 诱导的人类肌瘤病毒抗性蛋白 1(MXA)在肾小球中的表达,这种表达在肾小球内皮细胞中尤为明显。2/3的患者外周血中干扰素刺激基因的表达增加,所有三名患者的血清DNA酶活性都降低了。我们的研究结果表明,DNASE1L3相关肾小球肾炎可被纳入IFN I介导的肾脏疾病谱,并为IFN I导向疗法提供了理论依据,以改善这种罕见疾病的不良预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
American Journal of Kidney Diseases
American Journal of Kidney Diseases 医学-泌尿学与肾脏学
CiteScore
20.40
自引率
2.30%
发文量
732
审稿时长
3-8 weeks
期刊介绍: The American Journal of Kidney Diseases (AJKD), the National Kidney Foundation's official journal, is globally recognized for its leadership in clinical nephrology content. Monthly, AJKD publishes original investigations on kidney diseases, hypertension, dialysis therapies, and kidney transplantation. Rigorous peer-review, statistical scrutiny, and a structured format characterize the publication process. Each issue includes case reports unveiling new diseases and potential therapeutic strategies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信