Alternative complement pathway deregulation is correlated with dengue severity.
Alternative complement pathway deregulation is correlated with dengue severity.
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DOI：
10.1371/journal.pone.0006782
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发表时间：
2009-08-26
期刊：
影响因子：
3.7
通讯作者：
Marques ET
中科院分区：
文献类型：
--
作者：
Nascimento EJ;Silva AM;Cordeiro MT;Brito CA;Gil LH;Braga-Neto U;Marques ET
补体系统是连接先天免疫反应和获得性免疫反应的关键组成部分，有三条途径：经典途径、凝集素途径和替代途径。在本研究中，我们分析了登革热(DF)和登革出血热(DHF)患者血液样本中各种补体成分的水平，发现补体激活水平与疾病严重程度有关。与病情较轻的DF患者相比，DHF患者补体因子3(C3；p = 0.002)水平较低，C3a、C4a和C5a水平较高(p<；0.0001)。DF和DHF患者的C1q、免疫复合物(CIC-CIQ)和CRP水平无显著差异。然而，在MBL水平上检测到了微小但有统计学意义的差异。相反，替代途径的两种调节蛋白的水平在DF和DHF患者之间差异很大：DHF患者比DF患者有更高的D因子水平(p = 0.0 1)和更低的H因子水平(p = 0.0 3)，D因子分解因子B产生有活性的(C3bBb)C3转换酶，而H因子则使(C3bBb)C3转换酶失活。当我们将因子D和H的水平一起考虑作为(C3bBb)C3转换酶调节的指标时，我们发现DHF患者这些调节蛋白的水平有利于(C3bBb)C3转换酶的形成，而DF患者的(C3bBb)C3转换酶的形成受到抑制(p<；0.0001)。这些数据表明，调节因子D和H水平的失衡与DHF患者补体活性的异常调节有关。
The complement system, a key component that links the innate and adaptive immune responses, has three pathways: the classical, lectin, and alternative pathways. In the present study, we have analyzed the levels of various complement components in blood samples from dengue fever (DF) and dengue hemorrhagic fever (DHF) patients and found that the level of complement activation is associated with disease severity. Patients with DHF had lower levels of complement factor 3 (C3; p = 0.002) and increased levels of C3a, C4a and C5a (p<0.0001) when compared to those with the less severe form, DF. There were no significant differences between DF and DHF patients in the levels of C1q, immunocomplexes (CIC-CIq) and CRP. However, small but statistically significant differences were detected in the levels of MBL. In contrast, the levels of two regulatory proteins of the alternative pathway varied widely between DF and DHF patients: DHF patients had higher levels of factor D (p = 0.01), which cleaves factor B to yield the active (C3bBb) C3 convertase, and lower levels of factor H (p = 0.03), which inactivates the (C3bBb) C3 convertase, than did DF patients. When we considered the levels of factors D and H together as an indicator of (C3bBb) C3 convertase regulation, we found that the plasma levels of these regulatory proteins in DHF patients favored the formation of the (C3bBb) C3 convertase, whereas its formation was inhibited in DF patients (p<0.0001). The data suggest that an imbalance in the levels of regulatory factors D and H is associated with an abnormal regulation of complement activity in DHF patients.
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影响因子：
2.7
作者：
Acioli-Santos, Bartolomeu;Segat, Ludovica;Crovella, Sergio
通讯作者：
Crovella, Sergio
DOI：
10.1016/s0950-3536(05)80240-9
发表时间：
1995-03-01
期刊：
BAILLIERES CLINICAL HAEMATOLOGY
影响因子：
--
作者：
LARUSSA, VF;INNIS, BL
通讯作者：
INNIS, BL
DOI：
10.1073/pnas.0507320102
发表时间：
2005-10-18
影响因子：
11.1
作者：
Cummings, DAT;Schwartz, IB;Burke, DS
通讯作者：
Burke, DS
影响因子：
3.7
作者：
Cordeiro MT;Braga-Neto U;Nogueira RM;Marques ET Jr
通讯作者：
Marques ET Jr
影响因子：
5.3
作者：
Harboe M;Mollnes TE
通讯作者：
Mollnes TE