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Malaria Journal
Published in: Malaria Journal 1/2018

Open Access 01-12-2018 | Research

Host genetic polymorphisms and serological response against malaria in a selected population in Sri Lanka

Authors: Rajika L. Dewasurendra, Anna Jeffreys, Sharmini A. Gunawardena, Naduviladath V. Chandrasekharan, Kirk Rockett, Dominic Kwiatkowski, Nadira D. Karunaweera

Published in: Malaria Journal | Issue 1/2018

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Abstract

Background

Antibodies against the merozoite surface protein 1-19 (MSP1-19) and the apical membrane antigen 1 (AMA1) of the malaria parasite (Plasmodium vivax) are proven to be important in protection against clinical disease. Differences in the production/maintenance of antibodies may be due to many factors including host genetics. This paper discusses the association of 4 anti-malarial antibodies with selected host genetic markers.

Methods

Blood was collected from individuals (n = 242) with a history of malaria within past 15 years for DNA and serum. ELISA was carried out for serum to determine the concentration of anti-malarial antibodies MSP1-19 and AMA1 for both vivax and falciparum malaria. 170 SNPs related to malaria were genotyped. Associations between seropositivity, antibody levels and genetic, non-genetic factors were determined.

Results

Age ranged 13–74 years (mean age = 40.21 years). Majority were females. Over 90% individuals possessed either one or more type(s) of anti-malarial antibodies. Five SNPs were significantly associated with seropositivity. One SNP was associated with MSP1-19_Pv(rs739718); 4 SNPs with MSP1-19_Pf (rs6874639, rs2706379, rs2706381 and rs2075820) and1 with AMA1_Pv (rs2075820). Eleven and 7 genotypes (out of 15) were significantly associated with either presence or absence of antibodies. Three SNPs were found to be significantly associated with the antibody levels viz. rs17411697 with MSP1-19_Pv, rs2227491 with AMA1_Pv and rs229587 with AMA1_Pf. Linkage of the markers in the two groups was similar, but lower LOD scores were observed in seropositives compared to seronegatives.

Discussion and conclusions

The study suggests that several SNPs in the human genome that exist in Sri Lankan populations are significantly associated with anti-malarial antibodies, either with generation and/or maintenance of antibodies for longer periods, which can be due to either individual polymorphisms or most probably a combined effect of the markers.
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Literature
1.
2.
3.
Karunaweera ND, Galappaththy GN, Wirth DF. On the road to eliminate malaria in Sri Lanka: lessons from history, challenges, gaps in knowledge and research needs. Malar J. 2014;13:59.PubMedPubMedCentralCrossRef
4.
5.
6.
Akpogheneta O, Duah N, Tetteh K, Dunyo S, Lanar D, Pinder M, et al. Duration of naturally acquired antibody response to blood stage Plasmodium falciparum is age dependent and antigen specific. Infect Immun. 2008;76:1748–55.PubMedPubMedCentralCrossRef
7.
Dewasurendra RL, Suriyaphol P, Fernando SD, Carter R, Rockett K, Corran PH, et al. Genetic polymorphisms associated with anti-malarial antibody levels in a low and unstable malaria transmission area in southern Sri Lanka. Malar J. 2012;11:281.PubMedPubMedCentralCrossRef
8.
Siddiqui W, Tam LQ, Kramer KJ, Hui GS, Case SE, Yamaga KM, et al. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 1987;84:3014–8.PubMedCrossRefPubMedCentral
9.
Chappel JA, Holder AA. Monoclonal antibodies that inhibit Plasmodium falciparum invasion in vitro recognise the firstr growth factor-like domain of merozoite surface protein-1. Mol Biochem Parasit. 1993;60:303–11.CrossRef
10.
Daly TM, Long CA. A recombinant 15-kD carboxyl-terminal fragment of Plasmodium yoelii yoelii 17XL merozoite surface protein 1 induces a protective immune response in mice. Infect Immun. 1993;61:2462–7.PubMedPubMedCentral
11.
Branch OH, Udhayakumar V, Hightower AW, Oloo AJ, Hawley WA, Nahlen BL, et al. A longitudinal investigation of IgG and IgM antibody responses to the merozoite surface protein-1 19 kD domain of Plasmodium falciparum in pregnant women and infants: associations with febrite illness, parasitemia and anemia. Am J Trop Med Hyg. 1998;58:211–9.PubMedCrossRef
12.
Egan AF, Morris J, Barnish G, Allen S, Greenwood BM, Kaslow DC, et al. Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1. J Infect Dis. 1996;173:765–9.PubMedCrossRef
13.
Osier FHA, Fegan G, Polley SD, Murungi L, Verra F, Tetteh KKA, et al. Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect Immun. 2008;76:2240–8.PubMedPubMedCentralCrossRef
14.
Riley E, Allen S, Wheeler J, Blackman M, Bennett S, Takacs B, et al. Naturally aquired cellular and humoral immune response to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity. Parasite Immunol. 1992;14:321–37.PubMedCrossRef
15.
Remarque EJ, Faber BW, Kocken CHM, Thomas AW. Apical membrane antigen-1: a malaria vaccine candidate in review. Trends Parasitol. 2008;24:74–84.PubMedCrossRef
16.
MacRaild CS, Anders RF, Foley M, Norton RS. Apical membrane antigen-1 as an anti-malarial drug target. Curr Top Med Chem. 2011;11:2039–47.PubMedCrossRef
17.
Dodoo D, Aikins A, Kusi KA, Lamptey H, Remarque E, Milligan P, et al. Cohort study of the association of antibody levels to AMA1, MSP119, MSP3 and GLURP with protection from clinical malaria in Ghanaian children. Malar J. 2008;7:142.PubMedPubMedCentralCrossRef
18.
Nebie I, Diarra A, Ouedraogo A, Soulama I, Bougouma EC, Tiono AB, et al. Humoral response to Plasmodium falciparum blood-stage antigens and association with incidence of clincal malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun. 2008;76:759–66.PubMedCrossRef
19.
Sjoberg K, Lepers J, Raharimalala L, Larsson A, Olerup O, Marbiah N, et al. Genetic regulation of human anti-malarial antiboies in twins. Proc Natl Acad Sci USA. 1992;89:2101–4.PubMedCrossRefPubMedCentral
20.
Luoni G, Verra F, Arca B, Sirima BS, Troye-Blomberg M, Coluzzi M, et al. Antimalarial antibody levels and IL4 polymorphism in the Fulani of West Africa. Genes Immun. 2001;2:411–4.PubMedCrossRef
21.
Afridi S, Atkinson A, Garnier S, Fumoux F, Rihet P. Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso. Malar J. 2012;11:308.PubMedPubMedCentralCrossRef
22.
Shelton J, Corran P, Kwiatkowski D, Karunaweera N, Dewasurendra RL. MalariaGEN. Genetic determinants of anti-malarial acquired immunity in a large multi-centre study. Malar J. 2015;14:333.PubMedPubMedCentralCrossRef
23.
24.
Dewasurendra RL, Dias JN, Sepulveda N, Gunawardena GSA, Chandrasekharan N, Drakeley C, et al. Effectiveness of a serological tool to predict malaria transmission intensity in an elimination setting. BMC Infect Dis. 2017;17:49.PubMedPubMedCentralCrossRef
25.
26.
Zhang L, Cui X, Schmitt K, Hubert R, Navidi W, Arnheim N. Whole genome amplification from a single cell: implications for genetic analysis. Proc Natl Acad Sci USA. 1992;89:5847–51.PubMedCrossRefPubMedCentral
27.
Barrett J, Fry B, Maller J, Daly M. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.PubMedCrossRef
28.
Gabriel S, Schaffner S, Nguyen H, Moor J, Roy J, Blumenstiel B, et al. The structure of haplotype blocks in the human genome. Science. 2002;296:2225–9.PubMedCrossRef
29.
Drakeley C, Corran PH, Coleman P, Tongren JE, McDonald SLR, Carneiro I, et al. Estimating medium and long term trends in malaria transmission by using serological markers of malaria exposure. Proc Natl Acad Sci USA. 2005;102:5108–13.PubMedCrossRefPubMedCentral
30.
Warren M, Collins W, Jeffery G, Skinner J. The seroepidemiology of malaria in Middle America II. Studies on the Pacific coast of Costa Rica. Am J Trop Med Hyg. 1975;24:749–54.PubMedCrossRef
31.
Ondigo B, Hodges JS, Ireland KF, Magak NG, Lanar DE, Datta S, et al. Estimation of recent and long-term malaria transmission in a population by antibody testing to multiple Plasmodium falciparum antigens. J Infect Dis. 2014;210:1123–32.PubMedPubMedCentralCrossRef
32.
Warren M, Collins W, Cedillos R, Jeffery G. The seroepidemiology of malaria in Middle America III. Serologic assessment of localized Plasmodium falciparum epidemics. Am J Trop Med Hyg. 1976;25:20–5.PubMedCrossRef
33.
Manz R, Hauser A, Redbruch A. Maintenance of serum antibody levels. Annu Rev Immunol. 2005;23:367–86.PubMedCrossRef
34.
Druilhe P, Pradier O, Marc JP, Miltgen F, Mazier D, Parent G. Levels of antibodies to Plasmodium falciparum sporozoite surface antigens reflect malaria transmission rates and are persistent in the absence of reinfection. Infect Immun. 1986;53:393–7.PubMedPubMedCentral
35.
Noland G, Hendle-Paterson B, Min X, Morrmann A, Vulule J, Narum D, et al. Low prevalence of antibodies to pre-erythrocytic but not blood stage Plasmodium falciparum antigens in an area of unstable malaria transmission compared to prevalence in an area of stable malaria transmission. Infect Immun. 2008;76:5721–8.PubMedPubMedCentralCrossRef
36.
Kinyanjui S, Convey D, Lanar D, Marsh K. IgG antibody responses to Plasmodium falciparum merozoite antgens in Kenyan children have a short half-life. Malar J. 2007;6:82.PubMedPubMedCentralCrossRef
37.
Mendis C, Gamage-Mendis AC, De Zoysa APK, Abhayawardena TA, Carter R, Herath PRJ, et al. Characteristics of malaria transmission in Kataragama, Sri Lanka: a focus for immuno-epidemiological studies. Am J Trop Med Hyg. 1990;42:298–308.PubMedCrossRef
38.
Cutler D, Fung W, Krener M, Singhal M, Vogl T. Early life malaria exposure and adult outcomes: evidence from malaria eradication in India. Am Econ J Appl Econ. 2010;2:72–94.CrossRef
39.
Giha HA, Rosthoj S, Dodoo D, Haviid L, Satti GMH, Arnot DA, et al. The epidemiology of febrile malaria episodes in an area of unstable and seasonal transmission. Trans R Soc Trop Med Hyg. 2000;94:645–51.PubMedCrossRef
40.
Tongren JE, Drakeley CJ, McDonald SLR, Reyburn HG, Manjurano A, Nkya WMM, et al. Target antigen, age, and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria. Infect Immun. 2006;74:257–64.PubMedPubMedCentralCrossRef
41.
Weiss GE, Traore B, Kayentao K, Ongoiba A, Doumbo S, Doumtabe D, et al. The Plasmodium falciparum-specific human memory b cell compartment expands gradually with repeated malaria infections. PLoS Pathog. 2010;6:e1000912.PubMedPubMedCentralCrossRef
42.
Badu K, Afrane YA, Labri J, Stewart VA, Waitumbi J, Angov E, et al. Marked variation in MSP-119 antibody responses to malaria in western Kenyan highlands. BMC Infect Dis. 2012;12:50.PubMedPubMedCentralCrossRef
43.
Premaratna R, Galappaththy G, Chandrasena N, Fernando R, Nawasiwatte T, de Silva N, et al. Clinicians who practice in countries reaching malaria elimination, what should they be aware of: lessons learnt from recent experience in Sri Lanka. Malar J. 2011;10:302.PubMedPubMedCentralCrossRef
44.
Maiga B, Dolo A, Toure O, Dara V, Tapily A, Campino S, et al. Human candidate polymorphisms in sympatric ethnic groups dirrering in malaria susceptibility in Mali. PLoS ONE. 2013;8:e75675.PubMedPubMedCentralCrossRef
45.
Manjurano A, Clark T, Nadjm B, Mtove G, Wangal H, Sepulveda N, et al. Candidate human genetic polymorphisms and severe malaria in a Tanzanian population. PLoS ONE. 2012;7:e47463.PubMedPubMedCentralCrossRef
46.
Pagani F, Baralle F. Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genet. 2004;5:289–396.CrossRef
47.
48.
Greenwood TA, Kelsoe JR. Promotor and intronic variants affect the transcriptional regulation of the human dopamine transporter gene. Genomics. 2003;82:511–20.PubMedCrossRef
49.
Ostrovsky O, Grushchenko-Polaq AV, Beider K, Mayorov M, Canaani J, Shimoni A, et al. Identification of strong intron enhancer in the heparanase gene: effect of functional rs4693608 variant on HPSE enhancer actibity in hematological and solid malignancies. Oncogenesis. 2018;7:51.PubMedPubMedCentralCrossRef
50.
Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, et al. Ensembl 2018. Nucleic Acids Res. 2018;46:D754–61.PubMedCrossRef
51.
Spielmann M, Mundlos S. Looking beyond the genes: the role of non-coding variants in human disease. Hum Mol Genet. 2016;25:R157–65.PubMedCrossRef
52.
Naka I, Nishida N, Patarapotikul J, Nuchnoi P, Tokunaga K, Hananantachai H, et al. Identification of a haplotype block in the 5q31 cytokine gene cluster associated with the susceptibility to severe malaria. Malar J. 2009;8:232.PubMedPubMedCentralCrossRef
53.
Garcia A, Marquet S, Bucheton B, Hillaire D, Cot M, Fievet N, et al. Linkage analysis of blood Plasmodium falciparum levels: interest of the 5q31–q33 chromosome region. Am J Trop Med Hyg. 1998;58:705–9.PubMedCrossRef
54.
Flori L, Kumulungui B, Aucan C, Esnault C, Traore A, Fumoux F, et al. Linkage and association between Plasmodium falciparum blood infection levels and chromosome 5q31–q33. Genes Immun. 2003;4:265–8.PubMedCrossRef
55.
Prakash D, Fesel C, Jain R, Cazenave P, Mishra G, Pied S. Clusters of cytokines determine malaria severity in Plasmodium falciparum infected patients from endemic areas of central India. J Infect Dis. 2006;194:198–207.PubMedCrossRef
56.
Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J, et al. Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion. J Exp Med. 1994;179:703–8.PubMedCrossRef
57.
Giembycz MA, Lindsay M. Pharmocology of the eosinophil. Pharmocol Rev. 1999;51:216–339.
58.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.PubMedCrossRef
59.
Ockenhouse C, Hu W, Kester K, Cummings J, Stewart A, Heppner D, et al. Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria. Infect Immun. 2006;74:5561–73.PubMedPubMedCentralCrossRef
60.
Finney C, Lu Z, LeBourhis L, Philpott D, Kain K. Disruption of nod-like receptors alters inflammatory response to infection but does not confer protection in experimental cerebral malaria. Am J Trop Med Hyg. 2009;80:718–22.PubMedCrossRef
61.
Walley A, Aucan C, Kwiatkowski D, Hill A. Interleukin-1 gene cluster polymorphisms and susceptibility to clinical malaria in a Gambian case-control study. Eur J Hum Genet. 2004;12:132–8.PubMedCrossRef
62.
Koch O, Rockett K, Jallow M, Pinder M, Sisay-Joof F, Kwiatkowski D. Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region. Genes Immun. 2005;6:312–8.PubMedCrossRef
Metadata
Title
Host genetic polymorphisms and serological response against malaria in a selected population in Sri Lanka
Authors
Rajika L. Dewasurendra
Anna Jeffreys
Sharmini A. Gunawardena
Naduviladath V. Chandrasekharan
Kirk Rockett
Dominic Kwiatkowski
Nadira D. Karunaweera
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2018
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-018-2622-9

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