title: High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria.
abstract: BACKGROUND
  Cerebral malaria (CM) is responsible for most of the malaria-related deaths in children in sub-Saharan Africa. Although, not well understood, the pathogenesis of CM involves parasite and host factors which contribute to parasite sequestration through cytoadherence to the vascular endothelium. Cytoadherence to brain microvasculature is believed to involve host endothelial receptor, CD54 or intercellular adhesion molecule (ICAM)-1, while other receptors such as CD36 are generally involved in cytoadherence of parasites in other organs. We therefore investigated the contributions of host ICAM-1 expression and levels of antibodies against ICAM-1 binding variant surface antigen (VSA) on parasites to the development of CM.
  
  
  RESULTS
  Paediatric malaria patients, 0.5 to 13 years were recruited and grouped into CM and uncomplicated malaria (UM) patients, based on well defined criteria. Standardized ELISA protocol was used to measure soluble ICAM-1 (sICAM-1) levels from acute plasma samples. Levels of IgG to CD36- or ICAM-1-binding VSA were measured by flow cytometry during acute and convalescent states. Wilcoxon sign rank-test analysis to compare groups revealed association between sICAM-1 levels and CM (p<0.0037). Median levels of antibodies to CD36-binding VSA were comparable in the two groups at the time of admission and 7 days after treatment was initiated (p>0.05). Median levels of antibodies to CD36-binding VSAs were also comparable between acute and convalescent samples within any patient group. Median levels of antibodies to ICAM-1-binding VSAs were however significantly lower at admission time than during recovery in both groups.
  
  
  CONCLUSIONS
  High levels of sICAM-1 were associated with CM, and the sICAM-1 levels may reflect expression levels of the membrane bound form. Anti-VSA antibody levels to ICAM-binding parasites was more strongly associated with both UM and CM than antibodies to CD36 binding parasites. Thus, increasing host sICAM-1 levels were associated with CM whilst antibodies to parasite expressing non-ICAM-1-binding VSAs were not.
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana ; Department of Animal Biology and Conservation Science, University of Ghana, Legon, Accra, Ghana.
authors.forename: Selorme
authors.initials: S
authors.lastname: Adukpo
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Kwadwo A
authors.initials: KA
authors.lastname: Kusi
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ofori
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: John K A
authors.initials: JK
authors.lastname: Tetteh
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Amoako-Sakyi
authors.affiliation: Department of Child Health, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Bamenla Q
authors.initials: BQ
authors.lastname: Goka
authors.affiliation: Department of Child Health, University of Ghana Medical School, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: George O
authors.initials: GO
authors.lastname: Adjei
authors.affiliation: Department of Animal Biology and Conservation Science, University of Ghana, Legon, Accra, Ghana.
authors.forename: Dominic A
authors.initials: DA
authors.lastname: Edoh
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Bartholomew D
authors.initials: BD
authors.lastname: Akanmori
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Gyan
authors.affiliation: Immunology Department, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Accra, Ghana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dodoo
mesh_terms: D000293:Adolescent; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D018955:CD36 Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood* / Q000737:chemistry* / Q000276:immunology; D016779:Malaria, Cerebral / Q000097:blood*; D008297:Male; D010641:Phenotype; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D012044:Regression Analysis; D012995:Solubility
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018955:CD36 Antigens; D018799:Intercellular Adhesion Molecule-1