Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Antibody responses and Fc gamma receptor IIa polymorphism in relation to Plasmodium falciparum malaria
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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 [en]
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: urn:nbn:se:su:diva-27541ISBN: 978-91-7155-894-7 (print)OAI: oai:DiVA.org:su-27541DiVA: diva2:214659
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
List of papers
1. Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood-stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
Open this publication in new window or tab >>Fc gamma Receptor IIa (CD32) Polymorphism and Antibody responses to Asexual Blood-stage Antigens of Plasmodium falciparum Malaria in Sudanese Patients
Show others...
2007 (English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 66, no 1, 87-96 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25447 (URN)10.1111/j.1365-3083.2007.01947.x (DOI)000247478000011 ()
Available from: 2008-09-18 Created: 2008-09-11 Last updated: 2017-12-13Bibliographically approved
2. Differences in Fcγ receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali
Open this publication in new window or tab >>Differences in Fcγ receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali
Show others...
2008 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 7, no 175Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-25596 (URN)10.1186/1475-2875-7-175 (DOI)000260012000001 ()
Available from: 2008-11-06 Created: 2008-10-31 Last updated: 2017-12-13Bibliographically approved
3. FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan
Open this publication in new window or tab >>FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan
Show others...
2009 (English)In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 8, no 43, 1-10 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A SNP at position 131, in the FcgammaRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcgammaRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria. METHODS: Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcgammaRIIa-131 polymorphism. For comparison, 101 non-Fulani donors - (Masaleit, Hausa and Four) - living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses) to four malaria antigens (AMA-1, MSP 2 - 3D7 & FC27, Pf332-C231) were measured using indirect enzyme-linked immunosorbent assays. RESULTS: The FcgammaRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61-5.97, P value < 0.001). The Fulani showed lower anti-malarial IgG1 and IgG3 antibody levels as compared to the non-Fulani and higher levels of IgG2 antibodies. CONCLUSION: The FcgammaRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.

Place, publisher, year, edition, pages
BioMed Central Ltd., 2009
Keyword
Malaria, Fulani, disease susceptibility, Plasmodium falciparum, Fc gamma IIa, Antibody
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-27450 (URN)10.1186/1475-2875-8-43 (DOI)
Available from: 2009-05-05 Created: 2009-05-05 Last updated: 2017-12-13Bibliographically approved
4. Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan
Open this publication in new window or tab >>Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan
Show others...
2009 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 27, no 1, 62-71 p.Article in journal (Refereed) Published
Abstract [en]

Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children <5 years and reduced risk of severe malaria, while the responses of the IgG3 antibodies against MSP-2, MSP-3, GLURP in individuals above 5 years were bi-modal. A dominance of IgG3 antibodies in >5 years was also observed. In the final combined model, the highest levels of IgG1 antibodies to AMA-1, GLURP-R0, and the highest levels of IgG3 antibodies to 3D7 MSP-2 were independently associated with protection from clinical malaria. The study provides further support for the potential importance of the studied merozoite vaccine candidate antigens as targets for parasite neutralizing antibody responses of the IgG1 and IgG3 subclasses.

Place, publisher, year, edition, pages
Elsevier Ltd., 2009
Keyword
Malaria, Blood-stage antigens, Antibody
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-27451 (URN)10.1016/j.vaccine.2008.10.025 (DOI)000262156900011 ()
Available from: 2009-05-05 Created: 2009-05-05 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

fulltext(1586 kB)638 downloads
File information
File name FULLTEXT01.pdfFile size 1586 kBChecksum SHA-512
cb16731e8362d12d825b6caca917616b4a862daa767477aea65fe60d887c624c78c1848e455d7019666578e91e1a18b820d73acc5fc39de0a10169ef579432ae
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Iriemenam, Nnaemeka C.
By organisation
The Wenner-Gren Institute
Immunology in the medical area

Search outside of DiVA

GoogleGoogle Scholar
Total: 638 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 389 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf