Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets.
Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets.
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DOI：
10.1038/s41598-018-24462-4
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发表时间：
2018-04-19
影响因子：
4.6
通讯作者：
Plowe CV
中科院分区：
文献类型：
--
作者：
Travassos MA;Niangaly A;Bailey JA;Ouattara A;Coulibaly D;Lyke KE;Laurens MB;Pablo J;Jasinskas A;Nakajima R;Berry AA;Adams M;Jacob CG;Pike A;Takala-Harrison S;Liang L;Kouriba B;Kone AK;Rowe JA;Moulds J;Diallo DA;Doumbo OK;Thera MA;Felgner PL;Plowe CV
变异型表面抗原(VSA)在严重疟疾发病机制中起关键作用。确定患有严重疟疾的儿童对这些恶性疟原虫抗原的免疫差距或“漏洞”，将有助于我们更好地了解严重疟疾的脆弱性以及保护性免疫是如何发展的。利用含有来自三个VSA家族的179个抗原变体以及其他三个血液期恶性疟原虫抗原的300多个变体的蛋白质微阵列，检测了患有脑型疟疾或严重疟疾贫血的马里儿童和年龄匹配的对照组的血清中的反应性。与对照组相比，患有严重疟疾的儿童血清识别的细胞外PfEMP1片段较少，对特定片段的反应性也较低。从严重疟疾恢复后，恢复期血清对某些非CD36结合的PfEMP1的反应性增加，但对其他疟疾抗原没有。与患有脑型疟疾的儿童相比，患有严重疟疾贫血的儿童的血清对VSA的反应较少，而且这两组儿童的血清反应性图谱中都存在与患有脑型疟疾和严重疟疾贫血的儿童相同的空洞。这种基于微阵列的方法可能识别VSA的子集，从而为开发预防严重疾病的疫苗或预测高危儿童的诊断测试提供信息。
Variant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or “lacunae”, in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P. falciparum antigens, reactivity was measured in sera from Malian children with cerebral malaria or severe malarial anaemia and age-matched controls. Sera from children with severe malaria recognized fewer extracellular PfEMP1 fragments and were less reactive to specific fragments compared to controls. Following recovery from severe malaria, convalescent sera had increased reactivity to certain non-CD36 binding PfEMP1s, but not other malaria antigens. Sera from children with severe malarial anaemia reacted to fewer VSAs than did sera from children with cerebral malaria, and both of these groups had lacunae in their seroreactivity profiles in common with children who had both cerebral malaria and severe malarial anaemia. This microarray-based approach may identify a subset of VSAs that could inform the development of a vaccine to prevent severe disease or a diagnostic test to predict at-risk children.
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影响因子：
4.4
作者：
Cham, Gerald K. K.;Turner, Louise;Theander, Thor G.
通讯作者：
Theander, Thor G.
DOI：
10.1073/pnas.1120455109
发表时间：
2012-06-26
影响因子：
11.1
作者：
Lavstsen, Thomas;Turner, Louise;Theander, Thor G.
通讯作者：
Theander, Thor G.
影响因子：
3.7
作者：
Mwangi, Tabitha Wanja;Fegan, Gregory;Marsh, Kevin
通讯作者：
Marsh, Kevin
影响因子：
15.9
作者：
Chan, Jo-Anne;Howell, Katherine B.;Beeson, James G.
通讯作者：
Beeson, James G.
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ