Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

Abstract

Background: 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.

Methods: 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.

Results: 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.

Discussion: 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

Conclusions: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.

Figure 1

The figure shows the average number of malaria episodes experienced by the carriers of the major GM phenotypes; 1,17 5,14 (a) - 1,17 5,14,6 (b) - 1,17 5,13,14 (c) - 1,17 5,13,14,6 (d), during nine years of follow up in Daraweesh village. Comparing the carriers versus non-carrier of each of the 4 phenotypes, the only significant difference was that of 1,17 5,13,14,6 (d). The box represents 25-75 percentile, the horizontal line is the median value vertical bar is 95 percentile and open circle are the outliers

Figure 2

Concentrations (log 10) of total IgG and IgG isotypes to four antigens: MSP2-3D7, AMA-1, Pf332-C231 and MSP2-FC27. The figure demonstrates the significant differences in levels of the above antibodies between the each of the GM phenotype carriers; 1,17 5,14 - 1,17 5,14,6 - 1,17 5,13,14 - 1,17 5,13,14,6, and the corresponding-phenotype non-carriers.

Figure 3

Concentrations (log 10) of total IgG and IgG isotypes to two antigens: Pf332-C231 and MSP2-FC27. The figure demonstrates the significant differences in levels of the above antibodies between the each of the KM 1, 1,3 and 3 allotype carriers. The box represents 25-75 percentile, the horizontal line is the median value vertical bar is 95 percentile and open circle are the outliers. Only comparisons of statistically significant differences are presented