Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.
Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
Ticks Tick Borne Dis. 2019 Apr;10(3):639-646. doi: 10.1016/j.ttbdis.2019.02.003. Epub 2019 Feb 7.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by the SFTS virus (SFTSV) and has a high fatality rate. SFTSV-specific antibody profiles among patients with different clinical outcomes are yet to be described. The nucleocapsid protein (NP) is the most immunogenic viral antigen of the SFTSV. This study, therefore, sought to determine NP-specific antibody responses among SFTS patients with different disease progressions.
In the present study, 43 patients with confirmed SFTS were enrolled in our cohort, and 9 of them deceased. The clinical presentations and key laboratory parameters associated with SFTS fatality were also recorded. Serum samples from each patient were collected every 2 days during their hospitalization. NP-specific IgM and IgG responses as well as Gn or Gc-specific IgM responses were examined by enzyme-linked immunosorbent assay (ELISA), whereas, the dynamic viral loads of SFTSV RNA were quantified via real-time reverse transcription polymerase chain reaction (RT-PCR).
First, 77% of patients generated positive NP-specific IgM antibody responses within two weeks since illness onset, defined as 'N-specific IgM-positive patients', while the rest of the patients were termed as 'N-specific IgM-delayed patients'. Only 17% of the patients generated NP-specific IgG responses. The absence of NP-specific humoral responses was strongly associated with a high risk of fatality and severity of SFTS. IgM-positive patients had significantly lower levels of viral loads, less disturbed coagulopathy, and hepatic and cardiac damage compared to IgM-delayed patients. Moreover, compared to severe or fatal SFTS patients, mild SFTS patients had significantly higher magnitudes of NP-specific IgM responses, but not NP-specific IgG, Gn-specific IgM, or Gc-specific IgM responses. The abundance of NP-specific IgM responses negatively correlated with viral loads, coagulation disturbances, and hepatic injuries among SFTS patients.
Our data highlight distinct humoral profiles of NP-specific IgM responses among SFTS patients with different disease progressions and clinical outcomes.
严重发热伴血小板减少综合征（SFTS）是一种新发传染病，由 SFTS 病毒（SFTSV）引起，死亡率较高。不同临床结局的患者中 SFTSV 特异性抗体谱尚未得到描述。核衣壳蛋白（NP）是 SFTSV 最具免疫原性的病毒抗原。因此，本研究旨在确定不同疾病进展的 SFTS 患者中 NP 特异性抗体反应。
本研究纳入了 43 例确诊的 SFTS 患者，其中 9 例死亡。记录了与 SFTS 死亡相关的临床表现和关键实验室参数。每位患者在住院期间每 2 天采集一次血清样本。通过酶联免疫吸附试验（ELISA）检测 NP 特异性 IgM 和 IgG 反应以及 Gn 或 Gc 特异性 IgM 反应，通过实时逆转录聚合酶链反应（RT-PCR）定量 SFTSV RNA 的动态病毒载量。
首先，77%的患者在发病后两周内产生了阳性的 NP 特异性 IgM 抗体反应，定义为“N 特异性 IgM 阳性患者”，其余患者则被称为“N 特异性 IgM 延迟患者”。只有 17%的患者产生了 NP 特异性 IgG 反应。NP 特异性体液反应缺失与 SFTS 的高死亡率和严重程度密切相关。与 IgM 延迟患者相比，IgM 阳性患者的病毒载量显著降低，凝血障碍、肝和心脏损伤较轻。此外，与严重或致命的 SFTS 患者相比，轻度 SFTS 患者的 NP 特异性 IgM 反应幅度明显更高，但 NP 特异性 IgG、Gn 特异性 IgM 或 Gc 特异性 IgM 反应则不然。NP 特异性 IgM 反应的丰度与 SFTS 患者的病毒载量、凝血障碍和肝损伤呈负相关。
我们的数据突出了不同疾病进展和临床结局的 SFTS 患者中 NP 特异性 IgM 反应的不同体液特征。
