High plasma levels of soluble intercellular adhesion molecule (ICAM)-1 are associated with cerebral malaria

• Published in: PloS one 2013-12, Vol.8 (12), p.e84181-e84181
• Main Authors: Adukpo, Selorme, Kusi, Kwadwo A, Ofori, Michael F, Tetteh, John K A, Amoako-Sakyi, Daniel, Goka, Bamenla Q, Adjei, George O, Edoh, Dominic A, Akanmori, Bartholomew D, Gyan, Ben A, Dodoo, Daniel
• Format: Article
• Language: English
• Subjects: Adhesion; Adolescent; Analysis; Antibodies; Antibodies, Protozoan - immunology; Antigens, Protozoan - immunology; Binding; Biology; Blood; Brain; Brain research; CD36 antigen; CD36 Antigens - immunology; Cell adhesion; Cell adhesion & migration; Child; Child, Preschool; Children; Children & youth; Childrens health; Coma; Cytokines; Cytometry; Development and progression; Endothelium; Enzyme-linked immunosorbent assay; Erythrocytes; Female; Flow cytometry; Health sciences; Humans; Immunoglobulin G; Immunoglobulins; Immunology; Infant; Infections; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - blood; Intercellular Adhesion Molecule-1 - chemistry; Intercellular Adhesion Molecule-1 - immunology; Malaria; Malaria, Cerebral - blood; Male; Medical research; Medicine; Microvasculature; Organs; Parasites; Pathogenesis; Patients; Phenotype; Plasma; Plasma levels; Plasmodium falciparum; Plasmodium falciparum - immunology; Plasmodium falciparum - physiology; Proteins; Receptors; Regression Analysis; Solubility; Tumor necrosis factor-TNF; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084181

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. 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 (p0.05). 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. 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.