Abstract
BackgroundPlasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control.MethodsIn this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined.ResultsThe GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent.DiscussionThe results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptibleConclusionsThe GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.
Highlights
Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility
Protein polymorphism within the individual IgG subclasses is in part due to GM/KM allotypes, which are genetically determined serologically detectable antigenic determinants
The deployment of GM/KM allotyping for human population genetic analysis, mapping global haplotype distributions, indicated that selection on GM haplotypes is low at the human population level [6]
Summary
Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. Selection for resistance to malaria among inhabitants of malaria endemic regions may have influenced polymorphisms in genes encoding a variety of proteins involved in immunity [1]. Different subclasses of immunoglobulin G (IgG isotypes) have been proposed to play opposing roles in protection against malaria [2]. Levels, and switching between IgG isotypes is believed to play a role in development of protective immunity. Protein polymorphism within the individual IgG subclasses is in part due to GM/KM allotypes, which are genetically determined serologically detectable antigenic determinants. These allotypic determinants are expressed on both the heavy and light chains of IgG1, IgG2, and IgG3. It has been reported that the levels of the IgG subclasses are influenced by the GM allotypes in adult Caucasian blood donors [7] and in African American populations [8]
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