Elevated plasma levels of IgE in Plasmodium falciparum-primed individuals reflect an increased ratio of IL-4 to interferon-gamma (IFN-γ)-producing cells

Abstract

SUMMARYPeople living in Plasmodium falciparum-endemic areas frequently have elevated levels of total as well as P. falciparum-specific serum IgE. This study aimed at investigating whether the elevated serum IgE levels reflect a shift in the balance between CD4 + T helper 1 (Th1) and T helper 2 (Th2) cells in individuals naturally exposed to the P. falciparum parasite. To investigate the role of Th1 and Th2 cells in the human P. falciparum system we used the ELISPOT assay to determine the ratio of IFN-g-and IL-4-producing cells after specific antigen or mitogen activation in vitro. The donors were individuals who had acquired immunity through natural exposure to the parasite. In response to the specific malaria antigens, very few IL-4-producing cells were seen. However, in the response of individual donors to the polyclonal T cell activator, leucoagglutinin (La), the anti-malarial IgE levels in plasma were correlated with an increased ratio of IL-4/IFN-g producing cells. Thus, donors with ratios of IL-4/IFN-g > 1 exhibited mean plasma anti-malarial IgE levels significantly greater than those with ratios < 1. In individuals not living in P. falciparum-endemic areas the ratio of IL-4/IFN-g was always < 1. Taken together, our data suggest a shift in the balance between Th1 and Th2 cells in naturally P. falciparumprimed individuals, associated with elevated anti-P. falciparum plasma IgE levels. The role and biological significance of IgE (Th2-type immune response) for protection against P. falciparum and/or pathogenesis of malaria require further study.

The Role of Serum Immunoglobulin E in the Pathogenesis of Plasmodium falciparum Malaria in Ivorian Children

“…On the contrary, our results confirm those of several other authors [5][6][7][8][9] who observed higher IgE serum levels during the course of P. falciparum malaria. We could attribute this rise of the IgE serum level to a protector role during malarial infection, as Helmby and Perlmann [10,11] also reported.…”

Human immune responses to the highly repetitive Plasmodium falciparum antigen Pf332.

“…39 The role of IL-4 in the regulation of certain anti-malarial-specific antibodies is also indicated by the recently described association between an increased ratio of IL-4-/IFN-␥-producing cells and the presence of elevated anti-malarial IgE levels. 44 In the present study, donors having anti-peptide serum antibodies could be induced to produce IFN-␥ and IL-4. However, IFN-␥ and IL-4 have been shown to regulate isotype switching to different subclasses differently.…”

Impact of Mosquito Bites on Asexual Parasite Density and Gametocyte Prevalence in Asymptomatic Chronic Plasmodium falciparum Infections and Correlation with IgE and IgG Titers

“…The levels of P. falciparum-specific IgE are elevated during a malaria episode, and it was proposed previously that it plays a pathogenic role in severe episodes (20,38,39), whereas for asymptomatic infections, IgE levels were associated with protection (4). As described above, an important role for the Th1/Th2 balance in the outcome of infection was suggested previously by several studies (20).…”

“…The levels of P. falciparum-specific IgE are elevated during a malaria episode, and it was proposed previously that it plays a pathogenic role in severe episodes (20,38,39), whereas for asymptomatic infections, IgE levels were associated with protection (4). As described above, an important role for the Th1/Th2 balance in the outcome of infection was suggested previously by several studies (20). A recent genomewide linkage study identified several loci that were linked to asymptomatic parasite densities (44), and all these loci were previously linked to asthma/atopic disease or related phenotypes (e.g., see references 52 and 54).…”