{"title":"Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens","authors":"","doi":"10.1016/j.jinf.2024.106257","DOIUrl":null,"url":null,"abstract":"<div><p>Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations <em>in vitro</em>. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular <em>Plasmodium falciparum</em> erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001919/pdfft?md5=589220a4d5b1f25240cae5224ec2d351&pid=1-s2.0-S0163445324001919-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Infection","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163445324001919","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.
血红蛋白为 AC 或 AS 的儿童对临床疟疾的易感性降低。血红蛋白 C(Hb AC)或镰刀型血红蛋白(Hb AS)变异的红细胞在体外受感染红细胞表面的寄生虫变异表面抗原(VSA)呈递发生了改变。对于血红蛋白 AC 或镰状血红蛋白 AS 患者,不完全或改变的 VSA 表达对临床疟疾的保护作用尚不清楚。我们利用高通量蛋白芯片,试图用血清对VSAs的反应来衡量宿主暴露于Hb AC、Hb AS或野生型血红蛋白(Hb AA)的马里儿童中的VSAs的情况。在无并发症的疟疾中,与血红蛋白AA儿童相比,血红蛋白AC儿童对细胞外恶性疟原虫红细胞膜蛋白-1(PfEMP1)结构域的血清反应明显较低,但对细胞内PfEMP1结构域和其他VSAs(包括重复穿插家族(RIFIN)和次同源变异开放阅读框(STEVOR)家族成员)的反应没有差异。与血红蛋白 AA 儿童相比,血红蛋白 AC 和血红蛋白 AS 基因型的健康儿童能识别的细胞外 PfEMP1s 较少,尤其是与 CD36 结合的 PfEMP1s。这些降低的血清反应可能反映了血红蛋白 AC 或血红蛋白 AS 儿童的 VSA 表达减少或寄生虫暴露减少,并为保护机制提供了启示。
期刊介绍:
The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection.
Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.