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Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Shelton, Jennifer M. G., Corran, Patrick, Risley, Paul, Silva, Nilupa, Hubbart, Christina, Jeffreys, Anna, Rowlands, Kate, Craik, Rachel, Cornelius, Victoria, Hensmann, Meike, Molloy, Sile, Sepulveda, Nuno, Clark, Taane G., Band, Gavin, Clarke, Geraldine M., Spencer, Christopher C. A., Kerasidou, Angeliki, Campino, Susana, Auburn, Sarah, Tall, Adama and et al. (2015). Genetic determinants of anti-malarial acquired immunity in a large multi-centre study. Malaria Journal,14:1-18.

Document type: Journal Article
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IRMA ID 11381xPUB181
Title Genetic determinants of anti-malarial acquired immunity in a large multi-centre study
Author Shelton, Jennifer M. G.
Corran, Patrick
Risley, Paul
Silva, Nilupa
Hubbart, Christina
Jeffreys, Anna
Rowlands, Kate
Craik, Rachel
Cornelius, Victoria
Hensmann, Meike
Molloy, Sile
Sepulveda, Nuno
Clark, Taane G.
Band, Gavin
Clarke, Geraldine M.
Spencer, Christopher C. A.
Kerasidou, Angeliki
Campino, Susana
Auburn, Sarah
Tall, Adama
et al.
Journal Name Malaria Journal
Publication Date 2015
Volume Number 14
ISSN 1475-2875   (check CDU catalogue open catalogue search in new window)
Scopus ID 2-s2.0-84940473563
Start Page 1
End Page 18
Total Pages 18
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels.

Methods

Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP)4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels.

Results

Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)4 epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2.

Conclusion

Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.
Keywords Malaria
Antibody
Sickle cell trait
HbAS
CD36
Genotype
DOI http://dx.doi.org/10.1186/s12936-015-0833-x   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


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