Rapid humoral immune responses are required for recovery from haemorrhagic fever with renal syndrome patients

Haemorrhagic fever with renal syndrome (HFRS) following Hantaan virus (HTNV) infection displays variable clinical signs. Humoral responses elicited during HTNV infections are considered important, however, this process remains poorly understood. Herein, we have investigated the phenotype, temporal dynamics, and characteristics of B-cell receptor (BCR) repertoire in an HFRS cohort. The serological profiles were characterized by a lowered expression level of nucleoprotein (NP)-specific antibody in severe cases. Importantly, B-cell subsets were activated and proliferated within the first two weeks of symptom onset and moderate cases reacted more rapidly. BCR analysis in the recovery phase revealed a dramatic increase in the immunoglobulin gene diversity which was more significantly progressed in moderate infections. In severe cases, B-cell-related transcription was lower with inflammatory sets overactivated. Taken together, these data suggest the clinical signs and disease recovery in HFRS patients were positively impacted by rapid and efficacious humoral responses.汉坦病毒（Hantaan virus, HTNV）感染引发的肾综合征出血热（Haemorrhagic fever with renal syndrome, HFRS）临床表现具有显著异质性。汉坦病毒感染过程中诱导的体液免疫应答被认为具有重要作用，但目前对该过程的认知仍较为有限。本研究针对肾综合征出血热队列展开分析，对B细胞受体（B-cell receptor, BCR）库的表型、时序动态及特征进行了系统研究。血清学特征显示，重症患者体内核蛋白（nucleoprotein, NP）特异性抗体的表达水平显著下调。值得注意的是，症状发作后的前两周内，B细胞亚群即被激活并增殖，且中度症状患者的应答启动更为迅捷。恢复期的B细胞受体分析结果表明，免疫球蛋白基因多样性显著升高，且中度感染患者的该指标提升更为显著。重症患者的B细胞相关转录水平较低，而炎症相关基因集则处于过度激活状态。综上，本研究数据提示，快速且高效的体液免疫应答可对肾综合征出血热患者的临床症状改善与疾病康复产生正向促进作用。