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Association of the ICAM-1Kilifi mutation with protection against severe malaria in Lambaréné, Gabon
1Department of Parasitology, Institute of Tropical Medicine, University of Tübingen, Germany.
Abstract:
The intercellular adhesion molecule-1 (ICAM-1) is thought to be a receptor that mediates binding of Plasmodium falciparum-infected erythrocytes. Especially in vital organs, the binding of parasitized cells to the endothelium via ICAM-1 may lead to severe disease and death. Recently, a mutation in the coding region of ICAM-1, termed ICAM-1Kilifi, was described, causing a change from Lys to Met in the loop that interacts with rhinoviruses, lymphocytes, and parasitized red blood cells. Surprisingly, this mutation was shown to increase susceptibility of Kenyan children to severe malaria in one study. When we compared the distribution of ICAM-1Kilifi in two groups of Gabonese children enrolled in a case-control, matched-pair study who presented with either mild or severe malaria, we found that 55% of the patients with mild malaria were carriers whereas only 39% of those with severe malaria were carriers. The difference in the distribution of ICAM-1Kilifi homozygous pairs between the groups, as well as the distribution of ICAM-1Kilifi carriers, was statistically highly significant (P = 0.027 and P = 0.012, by the McNemar test). In a group of healthy school children from the same region, a distribution of 52% ICAM-1Kilifi carriers to 48% wild-type individuals was found. In a survey for the ICAM-1Kilifi in other malaria-endemic regions, this allele was also found in Nigeria and Papua New Guinea, but not in Thailand.
Insights
The ICAM-1Kilifi mutation, linked to severe malaria susceptibility, was found less frequently in Gabonese children with severe malaria compared to those with mild malaria. This suggests a protective effect against severe malaria in this population.
Area of Science:
- Immunogenetics
- Infectious Diseases
- Molecular Biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) mediates binding of Plasmodium falciparum-infected erythrocytes, potentially causing severe malaria.
- A specific ICAM-1 mutation, ICAM-1Kilifi, alters binding interactions and has been controversially linked to malaria susceptibility.
Purpose of the Study:
- To investigate the association between the ICAM-1Kilifi mutation and malaria severity in Gabonese children.
- To determine the distribution of ICAM-1Kilifi in different malaria endemic regions.
Main Methods:
- A case-control, matched-pair study comparing ICAM-1Kilifi distribution in children with mild versus severe malaria.
- Genotyping for the ICAM-1Kilifi allele in Gabonese children and healthy school children.
- Survey of ICAM-1Kilifi allele presence in Nigeria, Papua New Guinea, and Thailand.
Main Results:
- Children with mild malaria had a significantly higher prevalence of ICAM-1Kilifi carriers (55%) compared to those with severe malaria (39%).
- The ICAM-1Kilifi allele was present in healthy Gabonese school children (52% carriers).
- The ICAM-1Kilifi allele was detected in Nigeria and Papua New Guinea, but not in Thailand.
Conclusions:
- The ICAM-1Kilifi mutation appears to be associated with a reduced risk of severe malaria in Gabonese children.
- The geographical distribution of ICAM-1Kilifi suggests varying roles in malaria pathogenesis across different populations.
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