[Safe pregnancy and delivery in a female patient with systemic lupus erythematosus after discontinuation of dual-target chimeric antigen receptor T cells therapy].

Q3 Medicine
北京大学学报(医学版) Pub Date : 2024-12-18
Mingxia Wang, Ling Ding, Min Wang, Chanjuan Zou, Siyu Yan, Yingwen Liang, Weijia Wang, Shanzhi He
{"title":"[Safe pregnancy and delivery in a female patient with systemic lupus erythematosus after discontinuation of dual-target chimeric antigen receptor T cells therapy].","authors":"Mingxia Wang, Ling Ding, Min Wang, Chanjuan Zou, Siyu Yan, Yingwen Liang, Weijia Wang, Shanzhi He","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is a diffuse, systemic autoimmune disorder that can impact multiple organs and systems, with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum. It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE, as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity. Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions. In most instances, conventional treatment merely alleviates symptoms and necessitates lifelong immunotherapy. A limited number of clinical cases have explored chimeric antigen receptor T cells (CAR-T) therapy as a potential treatment for autoimmune diseases such as SLE. Research indicates that CAR-T can specifically target CD19 expressed on the surface of B cells and plasma cells, achieving profound depletion while minimizing drug-related side effects. This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team; following treatment, she ceased steroid and immunomodulator use, attaining sustained remission without these medications. The patient was a 23-year-old female. Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA (dsDNA) antibody and low complement C3. Renal biopsy in our hospital showed lupus nephritis Ⅳ-G (A/C), and National Institutes of Health (NIH) activity index (AI) score=4. She was diagnosed with \"SLE, lupus nephritis (LN)\". She was treated with hormones, immunosuppressants and Chinese medicine, but the effect was not good. After the CAR-T treatment, She stopped using hormones and immune agents and achieved continuous remission with zero hormones and zero immune agents. She became pregnant six months after CAR-T infusion, and gave birth to a healthy full-term, full-weight baby successfully. She is the first patient in China who successfully discontinued hormone, immune preparations and gave birth after CAR-T therapy. During the follow-up of the patient, we found that the immune indexes had basically returned to normal, and the safety was good. It indicates that CAR-T therapy may represent a promising and innovative therapeutic approach for the management of SLE. This offers hope and establishes a precedent for SLE women of childbearing age.</p>","PeriodicalId":8790,"journal":{"name":"北京大学学报(医学版)","volume":"56 6","pages":"1119-1125"},"PeriodicalIF":0.0000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652979/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"北京大学学报(医学版)","FirstCategoryId":"3","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

Abstract

Systemic lupus erythematosus (SLE) is a diffuse, systemic autoimmune disorder that can impact multiple organs and systems, with patients exhibiting abnormal levels of various autoantibodies and immune markers in their serum. It is currently understood that dysregulation of B cells activation plays a pivotal role in the pathogenesis of SLE, as aberrantly activated B cells produce autoantibodies that inflict damage on multiple organs through complement activation and antibody-dependent cell-mediated cyto-toxicity. Traditional therapies for SLE may prove ineffective for certain patients or lead to adverse reactions. In most instances, conventional treatment merely alleviates symptoms and necessitates lifelong immunotherapy. A limited number of clinical cases have explored chimeric antigen receptor T cells (CAR-T) therapy as a potential treatment for autoimmune diseases such as SLE. Research indicates that CAR-T can specifically target CD19 expressed on the surface of B cells and plasma cells, achieving profound depletion while minimizing drug-related side effects. This report details a female patient diagnosed with SLE and lupus nephritis who was successfully treated using dual-targeting B cells maturation antigen CAR-T by our research team; following treatment, she ceased steroid and immunomodulator use, attaining sustained remission without these medications. The patient was a 23-year-old female. Multiple examinations in other hospitals and in our hospital showed positive anti-double-stranded DNA (dsDNA) antibody and low complement C3. Renal biopsy in our hospital showed lupus nephritis Ⅳ-G (A/C), and National Institutes of Health (NIH) activity index (AI) score=4. She was diagnosed with "SLE, lupus nephritis (LN)". She was treated with hormones, immunosuppressants and Chinese medicine, but the effect was not good. After the CAR-T treatment, She stopped using hormones and immune agents and achieved continuous remission with zero hormones and zero immune agents. She became pregnant six months after CAR-T infusion, and gave birth to a healthy full-term, full-weight baby successfully. She is the first patient in China who successfully discontinued hormone, immune preparations and gave birth after CAR-T therapy. During the follow-up of the patient, we found that the immune indexes had basically returned to normal, and the safety was good. It indicates that CAR-T therapy may represent a promising and innovative therapeutic approach for the management of SLE. This offers hope and establishes a precedent for SLE women of childbearing age.

[停止双靶点嵌合抗原受体T细胞治疗后女性系统性红斑狼疮患者的安全妊娠和分娩]。
系统性红斑狼疮(SLE)是一种弥漫性系统性自身免疫性疾病,可影响多个器官和系统,患者血清中各种自身抗体和免疫标记物水平异常。目前了解到,B细胞活化失调在SLE的发病机制中起着关键作用,因为异常活化的B细胞产生自身抗体,通过补体活化和抗体依赖细胞介导的细胞毒性对多个器官造成损害。SLE的传统治疗方法可能对某些患者无效或导致不良反应。在大多数情况下,常规治疗只能缓解症状,需要终身免疫治疗。有限数量的临床病例已经探索了嵌合抗原受体T细胞(CAR-T)疗法作为自身免疫性疾病(如SLE)的潜在治疗方法。研究表明,CAR-T可以特异性靶向表达在B细胞和浆细胞表面的CD19,实现深度消耗,同时最小化药物相关副作用。本报告详细介绍了一位被诊断为SLE和狼疮肾炎的女性患者,我们的研究小组成功地使用双靶向B细胞成熟抗原CAR-T治疗;治疗后,她停止使用类固醇和免疫调节剂,在没有这些药物的情况下获得持续缓解。患者是一名23岁的女性。外院及本院多次检查均显示抗双链DNA (dsDNA)抗体阳性,补体C3低。我院肾活检示狼疮性肾炎Ⅳ-G (A/C),美国国立卫生研究院(NIH)活动指数(AI)评分=4。她被诊断为SLE,狼疮肾炎(LN)。她接受了激素、免疫抑制剂和中药治疗,但效果不佳。CAR-T治疗后,她停止使用激素和免疫药物,并在零激素和零免疫药物的情况下实现了持续缓解。她在CAR-T输注6个月后怀孕,并成功生下了一个健康的足月、全体重婴儿。她是中国第一个在CAR-T治疗后成功停用激素、免疫制剂并分娩的患者。在对患者的随访中,我们发现患者免疫指标基本恢复正常,安全性良好。这表明CAR-T疗法可能是一种有前景的、创新的SLE治疗方法。这为育龄SLE妇女提供了希望,并树立了先例。
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
北京大学学报(医学版)
北京大学学报(医学版) Medicine-Medicine (all)
CiteScore
0.80
自引率
0.00%
发文量
9815
期刊介绍: Beijing Da Xue Xue Bao Yi Xue Ban / Journal of Peking University (Health Sciences), established in 1959, is a national academic journal sponsored by Peking University, and its former name is Journal of Beijing Medical University. The coverage of the Journal includes basic medical sciences, clinical medicine, oral medicine, surgery, public health and epidemiology, pharmacology and pharmacy. Over the last few years, the Journal has published articles and reports covering major topics in the different special issues (e.g. research on disease genome, theory of drug withdrawal, mechanism and prevention of cardiovascular and cerebrovascular diseases, stomatology, orthopaedic, public health, urology and reproductive medicine). All the topics involve latest advances in medical sciences, hot topics in specific specialties, and prevention and treatment of major diseases. The Journal has been indexed and abstracted by PubMed Central (PMC), MEDLINE/PubMed, EBSCO, Embase, Scopus, Chemical Abstracts (CA), Western Pacific Region Index Medicus (WPR), JSTChina, and almost all the Chinese sciences and technical index systems, including Chinese Science and Technology Paper Citation Database (CSTPCD), Chinese Science Citation Database (CSCD), China BioMedical Bibliographic Database (CBM), CMCI, Chinese Biological Abstracts, China National Academic Magazine Data-Base (CNKI), Wanfang Data (ChinaInfo), etc.
×
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