免疫生物标志物用于预测血液系统恶性肿瘤患者对SARS-CoV-2疫苗的应答效果
Immune biomarkers to predict SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies
原文发布日期:2021-12-14
DOI: 10.1038/s41408-021-00594-1
类型: Article
开放获取: 是
英文摘要:
摘要翻译:
原文链接:
There is evidence of reduced SARS-CoV-2 vaccine effectiveness in patients with hematological malignancies. We hypothesized that tumor and treatment-related immunosuppression can be depicted in peripheral blood, and that immune profiling prior to vaccination can help predict immunogenicity. We performed a comprehensive immunological characterization of 83 hematological patients before vaccination and measured IgM, IgG, and IgA antibody response to four viral antigens at day +7 after second-dose COVID-19 vaccination using multidimensional and computational flow cytometry. Health care practitioners of similar age were the control group (n = 102). Forty-four out of 59 immune cell types were significantly altered in patients; those with monoclonal gammopathies showed greater immunosuppression than patients with B-cell disorders and Hodgkin lymphoma. Immune dysregulation emerged before treatment, peaked while on-therapy, and did not return to normalcy after stopping treatment. We identified an immunotype that was significantly associated with poor antibody response and uncovered that the frequency of neutrophils, classical monocytes, CD4, and CD8 effector memory CD127low T cells, as well as naive CD21+ and IgM+D+ memory B cells, were independently associated with immunogenicity. Thus, we provide novel immune biomarkers to predict COVID-19 vaccine effectiveness in hematological patients, which are complementary to treatment-related factors and may help tailoring possible vaccine boosters.
有证据表明血液系统恶性肿瘤患者接种SARS-CoV-2疫苗的有效性会降低。我们假设肿瘤及治疗相关的免疫抑制可通过外周血检测来表征,且接种前的免疫特征分析有助于预测免疫原性。我们对83例血液病患者在接种前进行了全面的免疫学特征分析,并采用多维计算流式细胞术检测了第二剂COVID-19疫苗接种后第7天针对四种病毒抗原的IgM、IgG和IgA抗体反应。年龄相近的医护人员作为对照组(n=102)。患者组中59种免疫细胞类型有44种发生显著改变;其中单克隆γ球蛋白病患者的免疫抑制程度高于B细胞疾病及霍奇金淋巴瘤患者。免疫失调在治疗前即出现,治疗期间达到高峰,且在停止治疗后未能恢复正常。我们发现一种与抗体反应低下显著相关的免疫表型,并揭示中性粒细胞、经典单核细胞、CD4与CD8效应记忆CD127低T细胞,以及初始CD21+与IgM+D+记忆B细胞的频率均独立影响免疫原性。因此,我们提出了新的免疫生物标志物,可用于预测血液病患者接种COVID-19疫苗的有效性,这些标志物与治疗相关因素互补,可能有助于制定个体化的疫苗加强接种策略。
……