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Human genetic factors involved in immunity to Plasmodium falciparum infection
Stockholm University, Faculty of Science, Wenner-Gren Institute for Experimental Biology.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This study investigated the associations between IL-4 -590 C/T and IL-10 -1087 A/G polymorphisms and malariometric indexes in the Fulani and the Dogon ethnic groups living in sympatry in Mali and differing in susceptibility to malaria. The correlations between antibodies level and parasitological data as well as splenomegaly were assessed. The impact of IL-4 -590 variants on the levels of the studied antibodies was also studied.

The allele and genotype frequencies of both studied SNPs differed significantly between the two groups. The Fulani IL-4 T allele carriers had a significantly higher infection prevalence compared with those carrying the CC genotype. No correlation between anti-malarial antibody levels and parasite prevalence was seen in any of the communities. In the Fulani, the increase in total IgE levels was related to the presence of infection. Malaria-specific IgG4 levels were negatively correlated to the number of clones within the Fulani. The Fulani IL-4 T allele carriers had higher total and malaria-specific IgE levels, compared to the CC genotype carriers. These results suggest that the amount of antibodies may not be the key element in the protection against malaria. IgG4 might be involved in protection against malaria. The impact of IL-4 -590 variants on the antibody levels may be affected by other genetic/epigenetic/epistatic or environmental factors.

In the study in Senegal, multiplicity of infection (MOI) increased after the transmission season in all subjects, except in α-thalassaemic and in G6PD-mutated children, suggesting that α-thalassaemia may protect against infection by certain parasite strains. G6PD-mutated individuals may resist against increase in MOI after the transmission season due to rapid clearance of infection at an early stage. HbAs and the ABO system do not affect MOI in asymptomatic individuals. MOI was positively correlated to parasitemia, and did not vary over age (in the range of 2 to 10 years). No relation between MOI and clinical attack was noted.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi , 2008. , 66 p.
Keyword [en]
Plasmodium falciparum, Malaria, Immunity, Ethnic groups, Mali, Senegal, Genetic factors, IL-4, IL-10, Polymorphism, MOI, RBC variants
National Category
Immunology
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-7555ISBN: 978-91-7155-614-1 (print)OAI: oai:DiVA.org:su-7555DiVA: diva2:198584
Public defence
2008-05-23, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-04-30 Created: 2008-04-30Bibliographically approved
List of papers
1. Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali
Open this publication in new window or tab >>Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali
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2007 (English)In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 9, no 9, 1043-1048 p.Article in journal (Refereed) Published
Abstract [en]

In this study, we compared the genotype and allele frequencies of the IL-10 -1087 A/G and IL-4 -590 C/T single nucleotide polymorphisms in asymptomatic subjects of two sympatric ethnic tribes differing in susceptibility to malaria, the Fulani and the Dogon in Mali. The genotype data was correlated with ethnicity and malariometric indexes. A statistically significant inter-ethnic difference in allele and genotype frequency for both loci was noted (P < 0.0001). Within the Fulani, the prevalence of Plasmodium falciparum infection, as detected by both microscopy and PCR, was associated with the IL-4 -590 T allele (P = 0.005 and P = 0.0005, respectively), whereas, no such associations were seen in the Dogon. Inter-ethnic differences in spleen rates, higher in the Fulani than the Dogon, were seen between T carriers (TT and CT) of both groups (P < 0.0001). Parasite densities and number of concurrent clones did not vary between IL-4 genotypes within any of the studied groups. These results suggest an association between the IL-4 -590 T allele and P. falciparum prevalence within the Fulani but not the Dogon. No associations between IL-10 genotypes and studied malariometric indexes were observed in any of the two communities.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-24953 (URN)10.1016/j.micinf.2007.04.011 (DOI)
Available from: 2008-04-30 Created: 2008-04-30 Last updated: 2011-12-14Bibliographically approved
2. Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali
Open this publication in new window or tab >>Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali
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2009 (English)In: Acta Tropica, ISSN 0001-706X, Vol. 9, no 1, 12-16 p.Article in journal (Refereed) Published
Abstract [en]

This study aimed to assess correlations between anti-malarial antibody levels and differences in malariometric characteristics, seen between two sympatric ethnic groups, the Fulani and the Dogon, living in Mali. Plasma levels of anti-malarial IgE, IgG. IgG1-4 and total IgE were determined in asymptomatic individuals, of the above mentioned groups, and were correlated to malariometric indexes. Significantly higher levels of anti-malarial IgE, IgG, IgG1-3 and total IgE were detected in the Fulani individuals as compared to the Dogon. No difference in plasma levels of malaria specific IgG4 was noted between the two groups. Within the Fulani, an increase in total IgE levels was associated with the presence of infection. As the IgG4 level increased, the number of clones decreased in the Fulani individuals. A positive correlation between elevated levels of anti-malarial IgG and IgG3 and splenomegaly was noted only within the Fulani group. No other correlations between antibody levels and parasite prevalence, clone numbers or spleen rates were observed in any of the communities. These results suggest that the magnitude of antibody response against Plasmodium falciparum may not be as important as it is believed to be. Instead, the fine specificity or function of the response might be more critical in protection against malaria disease.

Keyword
IgE; IgG; Ethnic groups; Malaria; Mali; P. falciparum
Identifiers
urn:nbn:se:su:diva-24954 (URN)10.1016/j.actatropica.2008.09.001 (DOI)000262150200003 ()
Note
Part of urn:nbn:se:su:diva-7555Available from: 2008-04-30 Created: 2008-04-30 Last updated: 2010-01-17Bibliographically approved
3. Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali
Open this publication in new window or tab >>Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali
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Manuscript (Other academic)
Identifiers
urn:nbn:se:su:diva-24955 (URN)
Note
Part of urn:nbn:se:su:diva-7555Available from: 2008-04-30 Created: 2008-04-30 Last updated: 2010-01-13Bibliographically approved
4. Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants
Open this publication in new window or tab >>Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants
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2008 In: Malaria Journal, ISSN 1475-2875, Vol. 7, no 17Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-24956 (URN)000254457900001 ()
Note
Part of urn:nbn:se:su:diva-7555Available from: 2008-04-30 Created: 2008-04-30Bibliographically approved

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