Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever
Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever
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DOI：
10.1086/507635
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发表时间：
2006-10-15
影响因子：
11.8
通讯作者：
King, Chwan-Chuen
中科院分区：
文献类型：
--
作者：
Wang, Wei-Kung;Chen, Hui-Ling;King, Chwan-Chuen
背景尽管先前的研究已经揭示了初始高水平的登革病毒复制对严重的和可能危及生命的疾病登革出血热（DHF）和登革休克综合征的贡献，但登革病毒在从发热到退热的过渡期间的免疫病理过程中的参与，这是决定登革出血热进展的关键阶段，尚未被认识到。以前，我们报道了登革病毒可以检测到登革出血热患者在此期间的免疫复合物。我们调查了54例登革热（一种相对温和的疾病）和49例DHF患者的血浆登革病毒载量、免疫复合物中的病毒、抗体应答、补体和细胞因子。这些病人已证实在2002年台湾南部的一次大规模爆发中感染了登革热病毒2型。登革出血热患者的病毒载量明显高于登革热患者，清除率也较慢。对于退热当天病毒载量> 5.7 log RNA拷贝/mL，DHF的阳性和阴性预测值分别为0.88和0.95。与登革热患者相比，登革出血热患者血清中登革病毒免疫复合物的水平更高，下降更慢，C5 a和可溶性白细胞介素2受体的水平也更高。这些发现表明，病毒载量和含病毒免疫复合物的清除速率较慢与随后的免疫激活相关，并有助于DHF在此关键阶段的进展。此外，退热当天的病毒载量可以预测DHF病例。
Background. Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immuopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period.Methods. We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever ( a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002.Results. Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads > 5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus containing immune complexes ( and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever.Conclusions. These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.