Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria
- Equal contributors
1 Department of Biochemistry, Faculty of Medicine and Medical Sciences, Arabian Gulf University (AGU), PO Box 26671, Manama, Kingdom of Bahrain
2 Malaria Research Center (MalRC), Department of Biochemistry and Department of Microbiology and Immunology, Faculty of Medicine, University of Khartoum, PO Box: 102, Khartoum, Sudan
3 Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden
4 Tropical Diseases Research Laboratory, Department of Medical Microbiology & Parasitology, College of Medicine, University of Lagos, PMB 12003 Lagos, Nigeria
5 Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
6 Faculty of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
7 Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
Malaria Journal 2009, 8:306 doi:10.1186/1475-2875-8-306Published: 22 December 2009
Plasmodium 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.
In 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.
The 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.
The 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 susceptible
The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.