Combined measurement of soluble and cellular ICAM-1 among children with Plasmodium falciparum malaria in Uganda.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Cserti-Gazdewich
Christine M
CM
Department of Laboratory Medicine & Pathobiology, University Health Network/University of Toronto, Canada. christine.cserti@uhn.on.ca
Dzik
Walter H
WH
Erdman
Laura
L
Ssewanyana
Isaac
I
Dhabangi
Aggrey
A
Musoke
Charles
C
Kain
Kevin C
KC
D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000276:immunology / Q000378:metabolism; D016779:Malaria, Cerebral / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000469:parasitology; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000302:isolation & purification; D012720:Severity of Illness Index; D012995:Solubility; D014454:Uganda / Q000453:epidemiology
D018799:Intercellular Adhesion Molecule-1