Antimalarial antibody levels and IL4 polymorphism in the Fulani of West Africa

Abstract

The Fulani are less clinically susceptible and more immunologically responsive to malaria than neighbouring ethnic groups. Here we report that anti-malarial antibody levels show a wide distribution amongst the Fulani themselves, raising the possibility that quantitative analysis within the Fulani may be an efficient way of screening for important genetic factors. The Th2 cytokine interleukin-4 is an obvious candidate: in Fulani, the IL4-524 T allele is at high frequency and is associated with elevated antibody levels against malaria antigens. These data highlight the possibility of combining inter- and intra-ethnic comparisons to characterize critical determinants of malarial immunity in a natural setting.

Genetic Complexity of Plasmodium Falciparum in Two Ethnic Groups of Burkina Faso With Marked Differences in Susceptibility to Malaria

“…The most likely explanation lies in the intrinsic characteristics of anti-malarial immune responses of the Fulani compared with the Mossi. 1,6,7 Candidate alleles of resistance genes that might be involved include IL4-524T, which was shown to be associated in this population with higher levels of P. falciparum specific IgG levels. 7 The lower number of clones in the Fulani versus the Mossi seen in our comparative analysis would then be consistent with the hypothesis that the Fulani are better able to control parasite infection due to non-specific immunomodulatory factors that could be more frequent in this population compared with other ethnic groups.…”

“…1 In the present study, we did not examine immunologic characteristics of the two ethnic groups, and have attributed the lower parasitologic and clinical P. falciparum indices among the Fulani compared with the Mossi to their stronger humoral and cellular immune responses against P. falciparum as reported in other villages in Burkina Faso. 6,7 In undertaking the current study, we wished to compare P. falciparum in the Fulani and Mossi in people of comparable age, status, and exposure to infection with similar parasite genotypes. We considered that the choice of two separate villages might have had an impact on any differences that might be observed, but this appears not to have been the case for the following reasons.…”

“…1,6 Interestingly, in the Fulani, but not in Mossi, higher IgG levels against P. falciparum were observed in association with a polymorphism in the promoter region of interleukin-4 (IL-4), a cytokine that plays a pivotal role in the regulation of antibody production. 7 Furthermore, IL-4 is localized in the 5q31-q33 chromosomal region, which has been shown to be linked to P. falciparum infection intensity in another study carried out in Burkina Faso. 8,9 There may be, therefore, a major determinant of resistance to malaria among the Fulani that is in linkage disequilibrium with the IL-4 promoter.…”

“…8,9 There may be, therefore, a major determinant of resistance to malaria among the Fulani that is in linkage disequilibrium with the IL-4 promoter. 7 In the current study, we examine whether the previously observed differences in malaria susceptibility between the Fulani and the Mossi have any impact on the genetic characteristics of their P. falciparum infections. Many previous surveys have established that a great complexity of P. falciparum clones occurs in infected inhabitants of different malariaendemic areas.…”

A single-nucleotide substitution from C to T at position −1055 in the IL-13 promoter is associated with protection from severe malaria in Thailand

“…9 More recently, this polymorphism was found to be associated with elevated antibody levels against malaria antigens in the Fulani of West Africa. 10 An IL-13 promoter polymorphism, IL-13 À1055C4T, is known to affect the expression level and to be associated with allergic asthma 11 and chronic obstructive pulmonary disease. 12 These observations raise the question of whether the IL-3 À16T4C, IL-4 À590C4T, and IL-13 À1055C4T polymorphisms are associated with severity of malaria.…”