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Differences in Fcγ receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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2008 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 7, no 175Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2008. Vol. 7, no 175
Identifiers
URN: urn:nbn:se:su:diva-25596DOI: 10.1186/1475-2875-7-175ISI: 000260012000001OAI: oai:DiVA.org:su-25596DiVA: diva2:200028
Available from: 2008-11-06 Created: 2008-10-31 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Host genetic factors and antibody responses with potential involvement in the susceptibility to malaria
Open this publication in new window or tab >>Host genetic factors and antibody responses with potential involvement in the susceptibility to malaria
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The relatively lower susceptibility to malaria seen in the Fulani ethnic group in Africa, as compared to other sympatric ethnic groups, has been related to genetic regulation of the immune responses. This thesis aimed to describe important pathways related to the regulation of antibodies in the immune responses during a malaria infection. Our results suggest that the higher anti-malarial immune responses seen in the Fulani are not a general hyper-responsiveness in this group, but neither a malaria specific response. Fcγ receptors are important structures in the immune responses, and polymorphisms in these genes were associated with IgG subclass levels, P. falciparum parasitemia and haemoglobin levels, suggesting that these polymorphisms may be a contributing factor to the differential susceptibility to malaria. C-reactive protein levels rise immediately in response to inflammatory stimuli, and the -286 CRP polymorphism was indicated to influence parasite levels, suggesting a possible involvement in the lower susceptibility to malaria seen in the Fulani ethnic group. Several cytokines are important in maintaining the optimal parasite-neutralizing milieu in the host, and we investigated polymorphisms in some of these cytokine genes, in order to establish a possible influence of these on malaria susceptibility. Several of these polymorphisms showed associations with haemoglobin levels, IgG subclass antibody levels and parasitemia, suggesting that IL-1β, IL-6, IL-10 and TNF could affect the susceptibility to malaria and the severity of the malaria infection.

Taken together, these data suggest that genetic factors have the ability to affect the antibody responses, and that several pathways can be affected. Moreover, the Fulani have a genetic predisposition for a higher inflammatory response during a malaria infection, which could lower their susceptibility to the disease. However, the control measures for this inflammation still have to be established and evaluated.

Place, publisher, year, edition, pages
Stockholm: Wenner-Grens institut för experimentell biologi, 2008. 85 p.
Keyword
Immunology
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-8301 (URN)978-91-7155-763-6 (ISBN)
Public defence
2008-11-28, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 10:00
Opponent
Supervisors
Available from: 2008-11-06 Created: 2008-10-31Bibliographically approved
2. Antibody responses and Fc gamma receptor IIa polymorphism in relation to Plasmodium falciparum malaria
Open this publication in new window or tab >>Antibody responses and Fc gamma receptor IIa polymorphism in relation to Plasmodium falciparum malaria
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immunity to asexual blood-stage of Plasmodium falciparum malaria is believed to be associated with protective antibodies of certain immunoglobulin classes and subclasses. This thesis addressed the importance of antibodies in relation to malaria infection and their effective interactions with Fc gamma receptor IIa (FcyRIIa) polymorphisms. Our data indicate that the frequency of FcyRIIa-R/R131 genotype was statistically significantly higher in Sudanese patients with severe malaria, while the FcyRIIa-H/H131 genotype showed a significant association with mild malaria. The levels of IgG1 and IgG3 subclass antibodies were statistically higher in the mild malaria patients.

The Fulani ethnic group in West Africa has been shown to be relatively resistant to malaria. We investigated the possible impact of FcyRIIa polymorphisms in the Fulani and non-Fulani in Mali and Sudan, and analysed their malaria-reactive IgG subclass profiles. The FcyRIIa-H/H131 genotype and H131-allele were found to be prevalent in the Fulani while R131-allele was prevalent in non-Fulani. The Fulani had higher serum levels of IgG1-3, with higher proportion of IgG2 than the non-Fulani.

Most clinico-epidemiology studies have been in areas with holo- and hyper-malaria endemicity. We have analysed antibody responses to a panel of six blood-stage antigens in relation to clinical malaria outcome in mesoendemic Sudan. Our results revealed a linear association with anti-AMA-1 IgG1 antibodies and reduced risk of severe malaria while a non-linear relationship with IgG3 antibodies was observed for MSP-2, MSP-3 and GLURP. In the combined final model, the highest levels of IgG1 subclass antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 subclass antibodies reactive to 3D7 MSP-2 were independently associated with a reduced risk of clinical malaria.

Taken together, these data suggest a possible association between FcyRIIa-R/H131 and anti-malarial antibody responses in the clinical outcome of malaria.

 

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2009. 86 p.
Keyword
malaria, Plasmodium falciparum, blood-stage, antibodies, antigens, logistic models, risk factors, age factors, merozoites, IgG subclasses, Fc gamma RIIa, single nucleotide polymorphism, ethnicity, endemicity, disease susceptibility
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-27541 (URN)978-91-7155-894-7 (ISBN)
Public defence
2009-06-03, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 B, 10:00 (English)
Opponent
Supervisors
Available from: 2009-05-13 Created: 2009-05-06 Last updated: 2009-05-13Bibliographically approved

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Iriemenam, Nnaemeka C.Troye-Blomberg, MaritaBerzins, Klavs
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