[Humoral response to Plasmodium falciparum antigenic peptides (MSP1, MSP2, and SR-11.1) in subjects living in endemic areas]. / La réponse humorale contre les peptides antigéniques de Plasmodium falciparum (MSP1, MSP2 et SR-11.1) chez des sujets vivant en zone endémique.

Introduction: vaccines are the key tools for controlling and eradicating malaria worldwide. Currently, research and development are focused on three types of vaccine candidates that target different life stages of Plasmodium falciparum in humans and the vector. The purpose of this study is to evaluate the humoral response to Plasmodium falciparum antigenic peptides (MSP1, MSP2 and SR-11.1) in subjects living in endemic areas. Methods: we conducted a cross-sectional study of serum samples collected from 182 Vietnamese subjects living in endemic areas over a period of 5 months. Whole blood was centrifuged and the serum was aliquoted into cryovials and preserved at -20°C until IgG testing. ELISA was used for total immunoglobulin G (IgG) antibodies testing after peptide coupling with glutaraldehyde. Results: a total of 182 sera samples from Vietnamese subjects living in endemic areas were included. In the different study age groups, total antigen-specific IgG antibodies against Plasmodium falciparum antigenic peptides (MSP-1; MSP-2 and SR-11.1) showed age-dependent distribution. In subjects aged 3-19 years, the level of total antigen-specific IgG antibodies against Plasmodium falciparum were lower than those of the age groups over 20 years of age (p=0.07). Comparison of specific antigen-specific IgG antibody levels with Plasmodium falciparum antigenic peptides MSP-1, MSP-2, and SR-11.1 in the age groups showed a significantly higher mean in MSP-1 and MSP-2 compared to anti-SR-11.1 (p=0.04). Conclusion: this study highlights that the level of specific antibodies against Plasmodium falciparum antigenic peptides (MSP-1; MSP-2 and SR-11.1) is age dependent. Of the three antigenic peptides, MSP-1 and MSP-2 appear to be more immunogenic than SR.11.1. Therefore, SR.11.1 is a macromolecule to the immune system and, from this point of view, appears to be significantly less immunogenic than other peptides.

Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso.

BACKGROUND: HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG) antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. METHODS: In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson's correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. RESULTS: After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i) haemoglobin C with IgG levels; ii) the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii) TNF-863 with IgG3 levels; iv) TNF-857 with IgG levels; and, v) TNF1304 with IgG3, IgG4, and IgG levels. CONCLUSION: Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual's humoral response against malaria.

Family-based association of a low producing lymphotoxin-alpha allele with reduced Plasmodium falciparum parasitemia.

Tumor necrosis factor (TNF)-related genes are thought to play a role in human malaria. TNF polymorphisms have been associated with severe malaria, mild malaria, and parasitemia. Lymphotoxin-alpha gene (LTA) that belongs to the TNF family is one such candidate gene. Here we report the family-based association analysis of a cis-regulatory lymphotoxin-alpha polymorphism with parasitemia in two independent populations living in Burkina Faso. Analysis of 199 subjects (34 families) living in an urban endemic area revealed the association of the low producing LTA+80A allele with reduced parasitemia. Furthermore, there was evidence of significant LTA+80-by-age and LTA+80-by-gender interactions. In another set of 318 residents (55 families) in a rural endemic area, we found both the association of the low producing LTA+80A allele with reduced parasitemia and LTA+80-by-age and LTA+80-by-gender interactions. This study suggests that LTA+80 polymorphism influences parasitemia and acts in an age- and gender-dependent manner.

Linkage of mild malaria to the major histocompatibility complex in families living in Burkina Faso.

Tumor necrosis factor alpha (TNF alpha) is thought to be a critical mediator of malaria fever, and mild malaria was previously reported to be linked to the MHC region containing the tumor necrosis factor alpha gene (TNF). Thirty-four families from Burkina Faso were analyzed to test for linkage between polymorphisms within the MHC region and mild malaria using the maximum-likelihood-binomial (MLB) program. Two-point analysis indicated linkage of mild malaria to TNFd (LOD = 3.27; P = 5.44 x 10(-5)). Using multipoint analysis, we also found evidence for linkage of mild malaria to the MHC region, with a peak close to TNF (LOD = 3.86; P = 1.22 x 10(-5)). Our results support genes within the MHC region being involved in mild malaria. In particular, the genetic variation within TNF may influence susceptibility to mild malaria. Nevertheless, TNF-238, TNF-244 and TNF-308 polymorphisms are unlikely to explain linkage of mild malaria to the MHC region, and the causal mutations remain to be identified.