不适合移植的大 B 细胞淋巴瘤二线使用 axicabtagene ciloleucel：ALYCANTE 最终分析
Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
在一位 B 细胞耗竭并伴有慢性 SARS-CoV-2 感染的淋巴瘤患者中，抗体和 CD8 T 细胞表位的突变积累
英文原题：Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection.
查看英文原题
Accumulation of mutations in antibody and CD8 T cell epitopes in a B cell depleted lymphoma patient with chronic SARS-CoV-2 infection.
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中文摘要
针对严重急性呼吸综合征冠状病毒-2（SARS-CoV-2）刺突蛋白的抗体可驱动慢性感染免疫功能低下患者体内的适应性进化。在此，我们对一名B细胞耗竭的淋巴瘤患者体内的SARS-CoV-2序列进行了纵向分析，该患者患有慢性且最终致命的感染，并鉴定出刺突蛋白中的三个突变，这些突变减弱了恢复期血浆介导的SARS-CoV-2中和作用。此外，在编码三个CD8 T细胞表位的非刺突区域出现了四个突变，其中包括一个受两个突变影响的核蛋白表位。与祖先肽相比，恢复期供者CD8 T细胞对每种突变肽的识别均降低，双突变产生叠加效应。查询公开的SARS-CoV-2序列显示，这些突变已在循环谱系中独立出现为同塑性。因此，我们的数据表明，CD8 T细胞对SARS-CoV-2突变的潜在影响，至少在体液免疫缺陷患者中，值得进一步研究以指导疫苗设计。
展开英文摘要原文
Antibodies against the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can drive adaptive evolution in immunocompromised patients with chronic infection.
Here we longitudinally analyze SARS-CoV-2 sequences in a B cell-depleted, lymphoma patient with chronic, ultimately fatal infection, and identify three mutations in the spike protein that dampen convalescent plasma-mediated neutralization of SARS-CoV-2.
Additionally, four mutations emerge in non-spike regions encoding three CD8 T cell epitopes, including one nucleoprotein epitope affected by two mutations. Recognition of each mutant peptide by CD8 T cells from convalescent donors is reduced compared to its ancestral peptide, with additive effects resulting from double mutations. Querying public SARS-CoV-2 sequences shows that these mutations have independently emerged as homoplasies in circulating lineages.
Our data thus suggest that potential impacts of CD8 T cells on SARS-CoV-2 mutations, at least in those with humoral immunodeficiency, warrant further investigation to inform on vaccine design.
论文信息
- 作者
- Khatamzas E、Antwerpen MH、Rehn A、Graf A、Hellmuth JC、Hollaus A、Mohr AW、Gaitzsch E
- 单位
- Department of Medicine III, University Hospital, Ludwig-Maximilians University Munich, Munich, Germany. elham.khatamzas@med.uni-heidelberg.de.Germany
- 文献类型
- 病例报告 · 非美国政府资助研究
- 期刊
- Nature communications2022 Sep 23
- 原文标识
- PubMed 36151076 · DOI 10.1038/s41467-022-32772-5
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