Department of Laboratory Medicine & Pathobiology, University Health Network/University of Toronto, Canada.
Malar J. 2010 Aug 16;9:233. doi: 10.1186/1475-2875-9-233.
Intercellular adhesion molecule-1 (ICAM-1) is a cytoadhesion molecule implicated in the pathogenesis of Plasmodium falciparum malaria. Elevated levels of soluble ICAM-1 (sICAM-1) have previously been reported with increased malaria disease severity. However, studies have not yet examined both sICAM-1 concentrations and monocyte ICAM-1 expression in the same cohort of patients. To better understand the relationship of soluble and cellular ICAM-1 measurements in malaria, both monocyte ICAM-1 expression and sICAM-1 concentration were measured in children with P. falciparum infection exhibiting a spectrum of clinical severity.
Samples were analysed from 160 children, aged 0.5 to 10.8 years, with documented P. falciparum malaria in Kampala, Uganda. The patients belonged to one of three pre-study defined groups: uncomplicated malaria (UM), severe non-fatal malaria (SM-s), and fatal malaria (SM-f). Subset analysis was done on those with cerebral malaria (CM) or severe malaria anaemia (SMA). Monocyte ICAM-1 was measured by flow cytometry. sICAM-1 was measured by enzyme immunoassay.
Both sICAM-1 and monocyte cell-surface ICAM-1 followed a log-normal distribution. Median sICAM-1 concentrations increased with greater severity-of-illness: 279 ng/mL (UM), 462 ng/mL (SM-s), and 586 ng/mL (SM-f), p < 0.0001. sICAM-1 levels were not statistically different among children with CM compared to SMA. Monocyte ICAM-1 expression was significantly higher in cases of UM compared with SM-s or SM-f (p < 0.001) and was higher among the subset of patients with CM compared with SMA, p < 0.0014. The combination of sICAM-1 and cellular ICAM-1 identified distinct categories of patients (UM with low sICAM-1 and higher monocyte ICAM-1, CM with both sICAM-1 and monocyte ICAM-1 high, and SMA with sICAM-1 high but monocyte ICAM-1 low).
In this cohort of children with P. falciparum malaria, sICAM-1 levels were associated with severity-of-illness. Patients with UM had higher monocyte ICAM-1 expression consistent with a role for monocyte ICAM-1 in immune clearance during non-severe malaria. Among the subsets of patients with either SMA or CM, monocyte ICAM-1 levels were higher in CM, consistent with the role of ICAM-1 as a marker of cytoadhesion. Categories of disease in pediatric malaria may exhibit specific combinations of soluble and cellular ICAM-1 expression.
细胞间黏附分子-1（ICAM-1）是一种细胞黏附分子，与恶性疟原虫疟疾的发病机制有关。可溶性细胞间黏附分子-1（sICAM-1）水平升高与疟疾疾病严重程度增加有关。然而，研究尚未在同一批患者中同时检测可溶性和细胞内 ICAM-1 浓度。为了更好地了解疟疾中可溶性和细胞性 ICAM-1 测量之间的关系，我们测量了患有恶性疟原虫感染的儿童的单核细胞 ICAM-1 表达和 sICAM-1 浓度，这些儿童的临床表现从无症状到严重非致命性疟疾（SM-s）和致命性疟疾（SM-f）不等。
从乌干达坎帕拉的 160 名年龄在 0.5 至 10.8 岁的患有记录在案的恶性疟原虫感染的儿童中采集样本。这些患者属于三种预先确定的研究组之一：无症状疟疾（UM）、严重非致命性疟疾（SM-s）和致命性疟疾（SM-f）。对伴有脑疟疾（CM）或严重疟疾贫血（SMA）的患者进行亚组分析。通过流式细胞术测量单核细胞 ICAM-1。通过酶联免疫吸附试验测量 sICAM-1。
sICAM-1 和单核细胞表面 ICAM-1 均呈对数正态分布。随着疾病严重程度的增加，sICAM-1 浓度中位数升高：279ng/ml（UM）、462ng/ml（SM-s）和 586ng/ml（SM-f），p<0.0001。与 SMA 相比，CM 患者的 sICAM-1 水平无统计学差异。与 SM-s 或 SM-f 相比，UM 患者的单核细胞 ICAM-1 表达明显更高（p<0.001），且 CM 患者的单核细胞 ICAM-1 表达明显高于 SMA 患者（p<0.0014）。sICAM-1 和细胞内 ICAM-1 的组合可识别不同的患者类别（UM 患者 sICAM-1 低但单核细胞 ICAM-1 高，CM 患者 sICAM-1 和单核细胞 ICAM-1 均高，SMA 患者 sICAM-1 高但单核细胞 ICAM-1 低）。
在本批患有恶性疟原虫疟疾的儿童中，sICAM-1 水平与疾病严重程度相关。UM 患者的单核细胞 ICAM-1 表达较高，这与单核细胞 ICAM-1 在非严重疟疾期间的免疫清除中发挥作用一致。在伴有 SMA 或 CM 的亚组患者中，CM 患者的单核细胞 ICAM-1 水平较高，这与 ICAM-1 作为细胞黏附标志物的作用一致。儿科疟疾的疾病类别可能表现出可溶性和细胞性 ICAM-1 表达的特定组合。
