Baker Virginia S, Imade Godwin E, Molta Norman B, Tawde Pallavi, Pam Sunday D, Obadofin Michael O, Sagay Soloman A, Egah Daniel Z, Iya Daniel, Afolabi Bangmboye B, Baker Murray, Ford Karen, Ford Robert, Roux Kenneth H, Keller Thomas Cs
Department of Biological Science, Florida State University, Tallahassee, Florida, USA.
Malar J. 2008 Feb 29;7:41. doi: 10.1186/1475-2875-7-41.
In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.
Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-gamma, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-beta and IL-10, and ANA were determined by immunoassay.
The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.
The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
在感染恶性疟原虫的儿童中，血细胞组织病理学、血浆成分、免疫能力发展与疾病严重程度之间的关系仍未得到充分了解。对患有非重症疟疾的尼日利亚儿童的血液进行分析，以深入了解这些关系。本研究提供了循环中性粒细胞胞外陷阱（NETs）和抗核IgG抗体（ANA）的证据。NETs和抗双链DNA的ANA的存在以及所发现的细胞因子谱表明，自身免疫机制可能在儿童中引发发病，但在成人中则起到免疫保护作用。
分析了从21名6岁以下患有非重症疟疾的尼日利亚儿童身上采集的外周血涂片载玻片和血样，这些儿童在开始使用磺胺多辛-乙胺嘧啶（SP）治疗前和治疗7天后的情况。载玻片用吉姆萨染色和DAPI染色。通过免疫测定法测定促炎细胞因子IFN-γ、IL-2、TNF、CRP和IL-6、选择的抗炎细胞因子TGF-β和IL-10以及ANA的水平。
这些儿童表现出带有附着寄生虫和红细胞的循环NETs、ANA水平升高、以Th2为主的细胞因子谱以及左移的白细胞分类计数。非特异性ANA水平在86%的儿童治疗前和100%的儿童SP治疗7天后显著，但在寄生虫传播低季节采集的年龄匹配对照样本中仅33%显著。治疗前和治疗后，81%的儿童中抗双链DNA的ANA水平均显著。
本研究结果表明，NET形成和抗双链DNA的ANA可能在感染恶性疟原虫的儿童中诱发病理，但在成人中激活针对恶性疟的保护机制。讨论了NETs中体内循环染色质和双链DNA ANA作为基于CpG寡核苷酸的疟疾疫苗低反应性的致病因素的意义。
