Table 5_Transcriptomic analysis after SARS-CoV-2 mRNA vaccination reveals a specific gene signature in low-responder hemodialysis patients.pdf

IntroductionIndividuals with comorbidities, such as chronic kidney disease and hemodialysis patients (HDP), are particularly susceptible to severe COVID-19 and to its complications. Furthermore, their immune response to vaccines is impaired, requiring tailored vaccination strategies. In this study, we investigated through transcriptomic profiling the immune response heterogeneity of HDP vaccinated with two doses of mRNA BNT162b2 vaccine.
MethodsTranscriptomic analyses were conducted in peripheral blood mononuclear cells (PBMC) collected from HDP and healthy controls (HC) before and 7 days after each dose. The HDP were stratified into high- and low-responders based on their humoral response after the second dose.
ResultsSignificant differences in gene expression related to B cell abundance and regulation, CD4 T cell proliferation, and inflammation pathways were observed at baseline and day 7 between HDP-low responders and HC, while the HDP high-responders displayed an intermediate expression profile for these genes.
DiscussionResults were consistent with the known immunologic alterations occurring in HDP cohorts related to lymphopenia, chronic inflammation, and dysregulated proliferation of CD4+. Our analyses identified an early transcriptional signature correlated with a diminished immune response in HDP low-responders, highlighting the importance of conducting a characterization of immunocompromised cohorts.

引言：伴有合并症的人群，例如慢性肾脏病患者与血液透析患者（hemodialysis patients，HDP），尤其易发展为重症新型冠状病毒肺炎（COVID-19）并出现相关并发症。此外，该人群对疫苗的免疫应答功能受损，因此亟需定制化的疫苗接种策略。本研究通过转录组谱分析，探究了接种两剂mRNA BNT162b2疫苗的HDP的免疫应答异质性。

方法：本研究于每剂疫苗接种前及接种后7天，采集HDP与健康对照（healthy controls，HC）的外周血单个核细胞（peripheral blood mononuclear cells，PBMC），并对其开展转录组分析。研究人员根据HDP在第二剂接种后的体液免疫应答情况，将其分为高应答者与低应答者两组。

结果：在基线期与接种后第7天，HDP低应答者与HC之间的基因表达存在显著差异，这些差异与B细胞丰度及调控、CD4 T细胞增殖以及炎症通路密切相关；而HDP高应答者的上述基因表达谱则呈中间状态。

讨论：本研究结果与已报道的HDP队列中存在的免疫学改变高度一致，这些改变与淋巴细胞减少症、慢性炎症及CD4+细胞增殖失调相关。本研究分析还鉴定出一种与HDP低应答者免疫应答减弱相关的早期转录特征，凸显了对免疫功能低下队列开展表征研究的重要价值。