Genetic determinants of anti-malarial acquired immunity in a large multi-centre study
Jennifer M G Shelton
(1)
,
Patrick Corran
(2, 3)
,
Paul Risley
(3)
,
Nilupa Silva
(3)
,
Christina Hubbart
(1)
,
Anna Jeffreys
(1)
,
Kate Rowlands
(1)
,
Rachel Craik
(1)
,
Victoria Cornelius
(1)
,
Meike Hensmann
(1)
,
Síle Molloy
(1)
,
Nuno Sepulveda
(2)
,
Taane Clark
(2)
,
Gavin Band
(1)
,
Geraldine Clark
(1)
,
Christopher C A Spencer
(1)
,
Angeliki Kerasidou
(4)
,
Susana Campino
(5)
,
Sarah Auburn
(1)
,
Adama Tall
(6)
,
Alioune Badara Ly
(6)
,
Odile Mercereau-Puijalon
(7)
,
Anavaj Sakuntabhai
(8)
,
Abdoulaye Djimde
(9)
,
Boubacar Maiga
(9)
,
Ousmane Toure
(9)
,
Ogobara Doumbo
(9)
,
Amagana Dolo
(9)
,
Marita Troye-Blomberg
(10)
,
Valentina D Mangano
(11)
,
Frederica Verra
(11)
,
David Modiano
(11)
,
Edith Bougouma
(12)
,
Sodiomon B Sirima
(12)
,
Muntaser E Ibrahim
(13)
,
Ayman Hussain
(13)
,
Nahid Eid
(13)
,
Abier Elzein
(13)
,
Hiba Mohammed
(13)
,
Ahmed Elhassan
(13)
,
Ibrahim Ibrahim
(13)
,
Thomas Williams
(14)
,
Carolyne Ndila
(14)
,
Alexander Macharia
(14)
,
Kevin Marsh
(14)
,
Alphaxard Manjurano
(2, 15)
,
Hugh Reyburn
(2, 15)
,
Martha Lemnge
(16)
,
Deus Ishengoma
(16)
,
Richard Carter
(17)
,
Nadira Karunaweera
(18)
,
Deepika Fernando
(18)
,
Rajika Dewasurendra
(18)
,
Christopher J Drakeley
(2, 15)
,
Eleanor M Riley
(2, 15)
,
Dominic Kwiatkowski
(1, 5)
,
Kirk Rockett
(1, 5)
,
Malariagen Consortium
1
The Wellcome Trust Centre for Human Genetics [Oxford]
2 LSHTM - London School of Hygiene and Tropical Medicine
3 NIBSC - National Institute for Biological Standards and Control
4 Nuffield Department of Population Health [Oxford]
5 The Wellcome Trust Sanger Institute [Cambridge]
6 Unité d'Epidémiologie des Maladies Infectieuses
7 Immunologie Moléculaire des Parasites
8 Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases
9 Malaria Research and Training Center [Bamako, Mali]
10 Stockholm University
11 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
12 CNRFP - Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso]
13 University of Khartoum
14 KWTRP - KEMRI-Wellcome Trust Research Programme
15 Tumaini University Makumira
16 NIMR - National Institute for Medical Research [Tanzania]
17 Edin. - University of Edinburgh
18 University of Colombo [Sri Lanka]
2 LSHTM - London School of Hygiene and Tropical Medicine
3 NIBSC - National Institute for Biological Standards and Control
4 Nuffield Department of Population Health [Oxford]
5 The Wellcome Trust Sanger Institute [Cambridge]
6 Unité d'Epidémiologie des Maladies Infectieuses
7 Immunologie Moléculaire des Parasites
8 Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases
9 Malaria Research and Training Center [Bamako, Mali]
10 Stockholm University
11 UNIROMA - Università degli Studi di Roma "La Sapienza" = Sapienza University [Rome]
12 CNRFP - Centre National de Recherche et de Formation sur le Paludisme [Ouagadougou, Burkina Faso]
13 University of Khartoum
14 KWTRP - KEMRI-Wellcome Trust Research Programme
15 Tumaini University Makumira
16 NIMR - National Institute for Medical Research [Tanzania]
17 Edin. - University of Edinburgh
18 University of Colombo [Sri Lanka]
Anavaj Sakuntabhai
- Fonction : Auteur
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- ORCID : 0000-0001-9099-6937
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Ogobara Doumbo
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Eleanor M Riley
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- ORCID : 0000-0003-3447-3570
Dominic Kwiatkowski
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Kirk Rockett
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Malariagen Consortium
- Fonction : Auteur
Résumé
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.
Origine | Publication financée par une institution |
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