Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Malaria Journal
Published in: Malaria Journal 1/2016

Open Access 01-12-2016 | Research

Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1)

Authors: Gustavo Capatti Cassiano, Adriana A. C. Furini, Marcela P. Capobianco, Luciane M. Storti-Melo, Maria E. Almeida, Danielle R. L. Barbosa, Marinete M. Póvoa, Paulo A. Nogueira, Ricardo L. D. Machado

Published in: Malaria Journal | Issue 1/2016

Login to get access

Abstract

Background

Humoral immune responses against proteins of asexual blood-stage malaria parasites have been associated with clinical immunity. However, variations in the antibody-driven responses may be associated with a genetic component of the human host. The objective of the present study was to evaluate the influence of co-stimulatory molecule gene polymorphisms of the immune system on the magnitude of the humoral immune response against a Plasmodium vivax vaccine candidate antigen.

Methods

Polymorphisms in the CD28, CTLA4, ICOS, CD40, CD86 and BLYS genes of 178 subjects infected with P. vivax in an endemic area of the Brazilian Amazon were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of IgM, total IgG and IgG subclasses specific for ICB2-5, i.e., the N-terminal portion of P. vivax merozoite surface protein 1 (PvMSP-1), were determined by enzyme-linked immuno assay. The associations between the polymorphisms and the antibody response were assessed by means of logistic regression models.

Results

After correcting for multiple testing, the IgG1 levels were significantly higher in individuals recessive for the single nucleotide polymorphism rs3116496 in CD28 (p = 0.00004). Furthermore, the interaction between CD28 rs35593994 and BLYS rs9514828 had an influence on the IgM levels (p = 0.0009).

Conclusions

The results of the present study support the hypothesis that polymorphisms in the genes of co-stimulatory components of the immune system can contribute to a natural antibody-driven response against P. vivax antigens.
Appendix
Available only for authorised users
Literature
1.
WHO. World malaria report. Geneva: World Health Organization; 2013.
2.
Gething PW, Elyazar IR, Moyes CL, Smith DL, Battle KE, Guerra CA, et al. A long neglected world malaria map: Plasmodium vivax endemicity in 2010. PLoS Negl Trop Dis. 2012;6:e1814.CrossRefPubMedPubMedCentral
3.
Lacerda MV, Mourão MP, Alexandre MA, Siqueira AM, Magalhães BM, Martinez-Espinosa FE, et al. Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature. Malar J. 2012;11:12.CrossRefPubMedPubMedCentral
4.
Goel VK, Li X, Chen H, Liu SC, Chishti AH, Oh SS. Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Proc Natl Acad Sci U S A. 2003;100:5164–9.CrossRefPubMedPubMedCentral
5.
Child MA, Epp C, Bujard H, Blackman MJ. Regulated maturation of malaria merozoite surface protein-1 is essential for parasite growth. Mol Microbiol. 2010;78:187–202.PubMedPubMedCentral
6.
Putaporntip C, Jongwutiwes S, Sakihama N, Ferreira MU, Kho WG, Kaneko A, et al. Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus. Proc Natl Acad Sci U S A. 2002;10:16348–53.CrossRef
7.
Soares IS, Levitus G, Souza JM, Del Portillo HA, Rodrigues MM. Acquired immune responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1 in individuals exposed to malaria. Infect Immun. 1997;65:1606–14.PubMedPubMedCentral
8.
Soares IS, da Cunha MG, Silva MN, Souza JM, Del Portillo HA, Rodrigues MM. Longevity of naturally acquired antibody responses to the N- and C-terminal regions of Plasmodium vivax merozoite surface protein 1. Am J Trop Med Hyg. 1999;60:357–63.PubMed
9.
Nogueira PA, Alves FP, Fernandez-Becerra C, Pein O, Santos NR, Pereira da Silva LH, et al. A reduced risk of infection with Plasmodium vivax and clinical protection against malaria are associated with antibodies against the N terminus but not the C terminus of merozoite surface protein 1. Infect Immun. 2006;74:2726–33.CrossRefPubMedPubMedCentral
10.
Storti-Melo LM, Souza-Neiras WC, Cassiano GC, Taveira LC, Cordeiro AJ, Couto VS, et al. Evaluation of the naturally acquired antibody immune response to the Pv200 L N-terminal fragment of Plasmodium vivax merozoite surface protein-1 in four areas of the Amazon Region of Brazil. Am J Trop Med Hyg. 2011;84(2 Suppl):58–63.CrossRefPubMedPubMedCentral
11.
Versiani FG, Almeida ME, Melo GC, Versiani FO, Orlandi PP, Mariúba LA, et al. High levels of IgG3 anti ICB2-5 in Plasmodium vivax-infected individuals who did not develop symptoms. Malar J. 2013;12:294.CrossRefPubMedPubMedCentral
12.
Riccio EK, Totino PR, Pratt-Riccio LR, Ennes-Vidal V, Soares IS, Rodrigues MM, et al. Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil. Malar J. 2013;12:326.CrossRefPubMedPubMedCentral
13.
Levitus G, Mertens F, Speranca MA, Camargo LM, Ferreira MU, del Portillo HA. Characterization of naturally acquired human IgG responses against the N-terminal region of the merozoite surface protein 1 of Plasmodium vivax. Am J Trop Med Hyg. 1994;51:68–76.PubMed
14.
Fernandez-Becerra C, Sanz S, Brucet M, Stanisic DI, Alves FP, Camargo EP, et al. Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay. Malar J. 2010;55:e67–74.
15.
Cavanagh DR, Dodoo D, Hviid L, Kurtzhals JA, Theander TG, Akanmori BD, et al. Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria. Infect Immun. 2004;72:6492–502.CrossRefPubMedPubMedCentral
16.
King CL, Michon P, Shakri AR, Marcotty A, Stanisic D, Zimmerman PA, et al. Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection. Proc Natl Acad Sci U S A. 2008;105:8363–8.CrossRefPubMedPubMedCentral
17.
Cole-Tobian JL, Michon P, Biasor M, Richards JS, Beeson JG, Mueller I, et al. Strain-specific Duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous Plasmodium vivax strains in Papua New Guinean children. Infect Immun. 2009;77:4009–17.CrossRefPubMedPubMedCentral
18.
Stanisic DI, Javati S, Kiniboro B, Lin E, Jiang J, Singh B, et al. Naturally acquired immune responses to P. vivax merozoite surface protein 3α and merozoite surface protein 9 are associated with reduced risk of P. vivax malaria in young Papua New Guinean children. PLoS Negl Trop Dis. 2013;7:e2498.CrossRefPubMedPubMedCentral
19.
Grimberg BT, Udomsangpetch R, Xainli J, McHenry A, Panichakul T, Sattabongkot J, et al. Plasmodium vivax invasion of human erythrocytes inhibited by antibodies directed against the Duffy binding protein. PLoS Med. 2007;4:e337.CrossRefPubMedPubMedCentral
20.
Vicentin EC, Françoso KS, Rocha MV, Iourtov D, Dos Santos FL, Kubrusly FS, et al. Invasion-inhibitory antibodies elicited by immunization with Plasmodium vivax apical membrane antigen-1 expressed in Pichia pastoris yeast. Infect Immun. 2014;82:1296–307.CrossRefPubMedPubMedCentral
21.
Beeson JG, Drew DR, Boyle MJ, Feng G, Fowkes FJ, Richards JS. Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria. FEMS Microbiol Rev. 2016;40:343–72.CrossRefPubMedPubMedCentral
22.
Gardner D, Jeffery LE, Sansom DM. Understanding the CD28/CTLA-4 (CD152) pathway and its implications for costimulatory blockade. Am J Transplant. 2014;14:1985–91.CrossRefPubMed
23.
Coyle AJ, Gutierrez-Ramos JC. The role of ICOS and other costimulatory molecules in allergy and asthma. Springer Semin Immunopathol. 2004;25:349–59.CrossRefPubMed
24.
Simpson TR, Quezada SA, Allison JP. Regulation of CD4 T cell activation and effector function by inducible costimulator (ICOS). Curr Opin Immunol. 2010;22:326–32.CrossRefPubMed
25.
Chatzigeorgiou A, Lyberi M, Chatzilymperis G, Nezos A, Kamper E. CD40/CD40L signaling and its implication in health and disease. BioFactors. 2009;35:474–83.CrossRefPubMed
26.
27.
Carpenter D, Abushama H, Bereczky S, Färnert A, Rooth I, Troye-Blomberg M, et al. Immunogenetic control of antibody responsiveness in a malaria endemic area. Hum Immunol. 2007;68:165–9.CrossRefPubMed
28.
Duah NO, Weiss HA, Jepson A, Tetteh KK, Whittle HC, Conway DJ. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens. PLoS ONE. 2009;4:e7381.CrossRefPubMedPubMedCentral
29.
Pandey JP, Morais CG, Fontes CJ, Braga EM. Immunoglobulin GM 3 23 5,13,14 phenotype is strongly associated with IgG1 antibody responses to Plasmodium vivax vaccine candidate antigens PvMSP1-19 and PvAMA-1. Malar J. 2010;9:229.CrossRefPubMedPubMedCentral
30.
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.CrossRefPubMedPubMedCentral
31.
Dewasurendra RL, Suriyaphol P, Fernando SD, Carter R, Rockett K, Corran P, 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.CrossRefPubMedPubMedCentral
32.
Lima-Junior JC, Rodrigues-da-Silva RN, Banic DM, Jiang J, Singh B, Fabrício-Silva GM, et al. Influence of HLA-DRB1 and HLA-DQB1 alleles on IgG antibody response to the P. vivax MSP-1, MSP-3α and MSP-9 in individuals from Brazilian endemic area. PLoS ONE. 2012;7:e36419.CrossRefPubMedPubMedCentral
33.
Storti-Melo LM, da Costa DR, Souza-Neiras WC, Cassiano GC, Couto VS, Póvoa MM, et al. Influence of HLA-DRB-1 alleles on the production of antibody against CSP, MSP-1, AMA-1, and DBP in Brazilian individuals naturally infected with Plasmodium vivax. Acta Trop. 2012;121:152–5.CrossRefPubMed
34.
Sabbagh A, Courtin D, Milet J, Massaro JD, Castelli EC, Migot-Nabias F, et al. Association of HLA-G 3’ untranslated region polymorphisms with antibody response against Plasmodium falciparum antigens: preliminary results. Tissue Antigens. 2013;82:53–8.CrossRefPubMed
35.
Ministério da Saúde. Secretaria de Vigilância em Saúde [Ministry of Health. Department of Health Surveillance]. Malária. Resumo epidemiológico de malária no Brasil. 2013 [Malaria. Epidemiological report of malaria in Brazil. 2013]. Sistema de Informações de Vigilância Epidemiológica (SIVEP). 2013. http://​portalweb04.​saude.​gov.​br/​sivep_​malaria. Accessed 27 Dec 2013.
36.
Cassiano GC, Furini AC, Capobianco MP, Storti-Melo LM, Cunha MG, Kano FS, et al. Polymorphisms in B cell co-stimulatory genes are associated with IgG antibody responses against blood–stage proteins of Plasmodium vivax. PLoS ONE. 2016;11:e0149581.CrossRefPubMedPubMedCentral
37.
Snounou G, Viriyakosol S, Jarra W, Thaithong S, Brown KN. Identification of the four human malaria parasite species in field samples by the polymerase chain reaction and detection of a high prevalence of mixed infections. Mol Biochem Parasitol. 1993;58:283–92.CrossRefPubMed
38.
Guzman VB, Morgun A, Shulzhenko N, Mine KL, Gonçalves-Primo A, Musatti CC, et al. Characterization of CD28, CTLA4, and ICOS polymorphisms in three Brazilian ethnic groups. Hum Immunol. 2005;66:773–6.CrossRefPubMed
39.
Malheiros D, Petzl-Erler ML. Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus. Genes Immun. 2009;10:547–58.CrossRefPubMed
40.
Gonzalez JR, Armengol L, Sole X, Guino E, Mercader JM, Estivill X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007;23:644–5.PubMed
41.
Feng S, Wang S, Chen CC, Lan L. GWAPower: a statistical power calculation software for genome-wide association studies with quantitative traits. BMC Genet. 2011;12:12.CrossRefPubMedPubMedCentral
42.
43.
Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMed
44.
45.
Cassiano GC, Santos EJ, Maia MH, Furini Ada C, Storti-Melo LM, Tomaz FM, et al. Impact of population admixture on the distribution of immune response co-stimulatory genes polymorphisms in a Brazilian population. Hum Immunol. 2015;76:836–42.CrossRefPubMed
46.
Conway DJ, Cavanagh DR, Tanabe K, Roper C, Mikes ZS, Sakihama N, et al. A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nat Med. 2000;6:689–92.CrossRefPubMed
47.
Polley SD, Tetteh KK, Cavanagh DR, Pearce RJ, Lloyd JM, Bojang KA, et al. Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria. Infect Immun. 2003;71:1833–42.CrossRefPubMedPubMedCentral
48.
Mertens F, Levitus G, Camargo LM, Ferreira MU, Dutra AP, Del Portillo HA. Longitudinal study of naturally acquired humoral immune responses against the merozoite surface protein 1 of Plasmodium vivax in patients from Rondonia, Brazil. Am J Trop Med Hyg. 1993;49:383–92.PubMed
49.
Bouharoun-Tayoun H, Oeuvray C, Lunel F, Druilhe P. Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J Exp Med. 1995;182:409–18.CrossRefPubMed
50.
Nasr A, Hamid O, Al-Ghamdi A, Allam G. Anti-malarial IgG subclasses pattern and FcγRIIa (CD32) polymorphism among pregnancy-associated malaria in semi-immune Saudi women. Malar J. 2013;12:110.CrossRefPubMedPubMedCentral
51.
Deloron P, Dubois B, Le Hesran JY, Riche D, Fievet N, Cornet M, et al. Isotypic analysis of maternally transmitted Plasmodium falciparum-specific antibodies in Cameroon, and relationship with risk of P. falciparum infection. Clin Exp Immunol. 1997;110:212–8.CrossRefPubMedPubMedCentral
52.
53.
Rummel T, Batchelder J, Flaherty P, LaFleur G, Nanavati P, Burns JM, et al. CD28 costimulation is required for the expression of T-cell-dependent cell-mediated immunity against blood-stage Plasmodium chabaudi malaria parasites. Infect Immun. 2004;72:5768–74.CrossRefPubMedPubMedCentral
54.
Elias RM, Sardinha LR, Bastos KR, Zago CA, da Silva AP, Alvarez JM, et al. Role of CD28 in polyclonal and specific T and B cell responses required for protection against blood stage malaria. J Immunol. 2005;174:790–9.CrossRefPubMed
55.
Taylor-Robinson AW, Smith EC. Modulation of experimental blood stage malaria through blockade of the B7/CD28 T-cell costimulatory pathway. Immunology. 1999;96:498–504.CrossRefPubMedPubMedCentral
56.
57.
Ihara K, Ahmed S, Nakao F, Kinukawa N, Kuromaru R, Matsuura N. Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with type 1 diabetes in the Japanese population. Immunogenetics. 2001;53:447–54.CrossRefPubMed
58.
Ivansson EL, Juko-Pecirep I, Gyllensten UB. Interaction of immunological genes on chromosome 2q33 and IFNG in susceptibility to cervical cancer. Gynecol Oncol. 2010;116:544–8.CrossRefPubMed
59.
Chen S, Zhang Q, Shen L, Liu Y, Xu F, Li D, et al. Investigation of CD28 gene polymorphisms in patients with sporadic breast cancer in a Chinese Han population in Northeast China. PLoS ONE. 2012;7:e48031.CrossRefPubMedPubMedCentral
60.
Ledezma-Lozano IY, Padilla-Martínez JJ, Leyva-Torres SD, Parra-Rojas I, Ramírez-Dueñas MG, Pereira-Suárez AL, et al. Association of CD28 IVS3 +17T/C polymorphism with soluble CD28 in rheumatoid arthritis. Dis Markers. 2011;30:25–9.CrossRefPubMedPubMedCentral
61.
Ferguson SE, Han S, Kelsoe G, Thompson CB. CD28 is required for germinal center formation. J Immunol. 1996;156:4576–81.PubMed
62.
Avery DT, Kalled SL, Ellyard JI, Ambrose C, Bixler SA, Thien M, et al. BAFF selectively enhances the survival of plasmablasts generated from human memory B cells. J Clin Invest. 2003;112:286–97.CrossRefPubMedPubMedCentral
63.
Liu XQ, Stacey KJ, Horne-Debets JM, Cridland JA, Fischer K, Narum D, et al. Malaria infection alters the expression of B-cell activating factor resulting in diminished memory antibody responses and survival. Eur J Immunol. 2012;42:3291–301.CrossRefPubMed
64.
Capobianco MP, Cassiano GC, Furini AA, Storti-Melo LM, Pavarino EC, Galbiatti AL, et al. No evidence for association of the CD40, CD40 L and BLYS polymorphisms, B-cell co-stimulatory molecules, with Brazilian endemic Plasmodium vivax malaria. Trans R Soc Trop Med Hyg. 2013;107:377–83.CrossRefPubMed
Metadata
Title
Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1)
Authors
Gustavo Capatti Cassiano
Adriana A. C. Furini
Marcela P. Capobianco
Luciane M. Storti-Melo
Maria E. Almeida
Danielle R. L. Barbosa
Marinete M. Póvoa
Paulo A. Nogueira
Ricardo L. D. Machado
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2016
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/s12936-016-1350-2

Other articles of this Issue 1/2016

Malaria Journal 1/2016 Go to the issue

Research

Genomic signatures of population decline in the malaria mosquito Anopheles gambiae

Research

Visualization of house-entry behaviour of malaria mosquitoes

Research

Community health workers adherence to referral guidelines: evidence from studies introducing RDTs in two malaria transmission settings in Uganda

Research

Operational challenges to continuous LLIN distribution: a qualitative rapid assessment in four countries

Research

Is Nigeria winning the battle against malaria? Prevalence, risk factors and KAP assessment among Hausa communities in Kano State

Research

A longitudinal study of the durability of long-lasting insecticidal nets in Zambia

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits