Transcriptomic analysis after SARS-CoV-2 mRNA vaccination reveals a specific gene signature in low-responder hemodialysis patients. Transcriptomic analysis after SARS-CoV-2 mRNA vaccination reveals a specific gene signature in low-responder hemodialysis patients

Individuals 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. Transcriptomic 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. Significant 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. Results 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. Overall design: to investigate the immune response of hemodialysis patients (HDP) vaccinated with the mRNA BNT162b2 vaccine through transcriptomic profiling Peripheral blood mononuclear cells (PBMC) were collected from HDP and healthy controls (HC) at baseline (day 0), at days 7, 21 (before the second dose) and 28 (7 days after the second dose) after two doses of mRNA BNT162b2 vaccine

合并基础疾病的人群，例如慢性肾脏病患者与血液透析患者（hemodialysis patients, HDP），对重症新型冠状病毒肺炎（COVID-19）及其并发症具有更高的易感性。此外，该人群对疫苗的免疫应答存在损伤，因此需要定制化的疫苗接种策略。
本研究通过转录组谱分析，对接种两剂mRNA BNT162b2疫苗的血液透析患者的免疫应答异质性进行了探究。研究在每剂接种前及接种后7天，采集血液透析患者与健康对照（healthy controls, HC）的外周血单个核细胞（peripheral blood mononuclear cells, PBMC）进行转录组分析。
研究人员根据第二剂接种后的体液免疫应答情况，将血液透析患者分为高应答者与低应答者亚组。在基线及第7天时，低应答血液透析患者与健康对照之间，在与B细胞丰度及调控、CD4阳性T细胞增殖以及炎症通路相关的基因表达上存在显著差异；而高应答血液透析患者的上述基因表达谱则呈中间型。
本研究结果与已报道的血液透析患者队列中存在的免疫学改变相符，包括淋巴细胞减少、慢性炎症以及CD4阳性T细胞增殖失调。本研究分析还鉴定出与低应答血液透析患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进行特征化研究的重要性。
【研究设计】本研究通过转录组谱分析，探究接种两剂mRNA BNT162b2疫苗的血液透析患者的免疫应答情况。研究分别在基线（第0天）、第7天、第21天（第二剂接种前）以及第28天（第二剂接种后7天）采集血液透析患者与健康对照的外周血单个核细胞（PBMC）。