Hemoglobin S and C Heterozygosity Enhances Neither the Magnitude nor Breadth of Antibody Responses to a Diverse Array of Plasmodium Falciparum Antigens

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2011 Oct 15

PMID 21998476

Citations 25

Authors

Xiaolin Tan

Boubacar Traore

Kassoum Kayentao

Aissata Ongoiba

Safiatou Doumbo

Michael Waisberg

Ogobara K Doumbo

Philip L Felgner

Rick M Fairhurst

Peter D Crompton

Affiliations

Soon will be listed here.

Abstract

Background: Heterozygous states of hemoglobin (Hb) A and HbS (HbAS, sickle-cell trait) or HbC (HbAC) protect against Plasmodium falciparum malaria by unclear mechanisms. Several studies suggest that HbAS and HbAC accelerate the acquisition of immunity to malaria, possibly by enhancing P. falciparum-specific antibody responses.

Methods: We used a protein microarray representing 491 P. falciparum proteins expressed during exoerythrocytic and erythrocytic stages of the life cycle to test the hypothesis that HbAS and HbAC enhance the P. falciparum-specific IgG response compared with normal HbAA. Plasma samples were collected from Malian children aged 2-10 years before and after a 6-month malaria season and were probed against the microarray. Immunoglobulin G (IgG) profiles of children with HbAA (n = 106), HbAS (n = 15), and HbAC (n = 20) were compared.

Results: Although the magnitude and breadth of P. falciparum-specific IgG responses increased with age and from before to after the malaria season in each antigen category, Hb type did not independently predict significant differences in P. falciparum-specific IgG profiles.

Conclusions: These data do not support the hypothesis that HbAS and HbAC protect against malaria by enhancing P. falciparum-specific antibody responses. It remains possible that HbAS and HbAC protect against malaria by enhancing antibody responses to antigens not studied here or through other immune mechanisms.

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References

Dicko A, Klion A, Thera M, Sagara I, Yalcouye D, Niambele M . The etiology of severe anemia in a village and a periurban area in Mali. Blood. 2004; 104(4):1198-200. DOI: 10.1182/blood-2003-11-3884. View

Aidoo M, Terlouw D, Kolczak M, McElroy P, Kuile F, Kariuki S . Protective effects of the sickle cell gene against malaria morbidity and mortality. Lancet. 2002; 359(9314):1311-2. DOI: 10.1016/S0140-6736(02)08273-9. View

Friedman M . Erythrocytic mechanism of sickle cell resistance to malaria. Proc Natl Acad Sci U S A. 1978; 75(4):1994-7. PMC: 392469. DOI: 10.1073/pnas.75.4.1994. View

Luty A, Ulbert S, Lell B, Lehman L, Schmidt-Ott R, Luckner D . Antibody responses to Plasmodium falciparum: evolution according to the severity of a prior clinical episode and association with subsequent reinfection. Am J Trop Med Hyg. 2001; 62(5):566-72. DOI: 10.4269/ajtmh.2000.62.566. View

Mackintosh C, Christodoulou Z, Mwangi T, Kortok M, Pinches R, Williams T . Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1. Malar J. 2008; 7:155. PMC: 2533674. DOI: 10.1186/1475-2875-7-155. View

RINGELHANN B, Hathorn M, JILLY P, Grant F, Parniczky G . A new look at the protection of hemoglobin AS and AC genotypes against plasmodium falciparum infection: a census tract approach. Am J Hum Genet. 1976; 28(3):270-9. PMC: 1685008. View

Allen S, Bennett S, Riley E, Rowe P, Jakobsen P, ODonnell A . Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia. Trans R Soc Trop Med Hyg. 1992; 86(5):494-8. DOI: 10.1016/0035-9203(92)90083-o. View

Le Hesran J, Personne I, Personne P, Fievet N, Dubois B, Beyeme M . Longitudinal study of Plasmodium falciparum infection and immune responses in infants with or without the sickle cell trait. Int J Epidemiol. 1999; 28(4):793-8. DOI: 10.1093/ije/28.4.793. View

Ntoumi F, Ekala M, Makuwa M, Lekoulou F, Mercereau-Puijalon O, Deloron P . Sickle cell trait carriage: imbalanced distribution of IgG subclass antibodies reactive to Plasmodium falciparum family-specific MSP2 peptides in serum samples from Gabonese children. Immunol Lett. 2002; 84(1):9-16. DOI: 10.1016/s0165-2478(02)00131-1. View

10.

Marsh K, Otoo L, Hayes R, Carson D, Greenwood B . Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans R Soc Trop Med Hyg. 1989; 83(3):293-303. DOI: 10.1016/0035-9203(89)90478-1. View

11.

Bayoumi R . The sickle-cell trait modifies the intensity and specificity of the immune response against P. falciparum malaria and leads to acquired protective immunity. Med Hypotheses. 1987; 22(3):287-98. DOI: 10.1016/0306-9877(87)90193-9. View

12.

Le Roch K, Zhou Y, Blair P, Grainger M, Moch J, Haynes J . Discovery of gene function by expression profiling of the malaria parasite life cycle. Science. 2003; 301(5639):1503-8. DOI: 10.1126/science.1087025. View

13.

Fleming A, Kagan I, Matsushima T, MOLINEAUX L . Abnormal haemoglobins in the Sudan savanna of Nigeria. II. Immunological response to malaria in normals and subjects with sickle cell trait. Ann Trop Med Parasitol. 1979; 73(2):173-83. DOI: 10.1080/00034983.1979.11687244. View

14.

Verra F, Simpore J, Warimwe G, Tetteh K, Howard T, Osier F . Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria. PLoS One. 2007; 2(10):e978. PMC: 1991593. DOI: 10.1371/journal.pone.0000978. View

15.

Cholera R, Brittain N, Gillrie M, Lopera-Mesa T, Diakite S, Arie T . Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin. Proc Natl Acad Sci U S A. 2008; 105(3):991-6. PMC: 2242681. DOI: 10.1073/pnas.0711401105. View

16.

Cabrera G, Cot M, Migot-Nabias F, Kremsner P, Deloron P, Luty A . The sickle cell trait is associated with enhanced immunoglobulin G antibody responses to Plasmodium falciparum variant surface antigens. J Infect Dis. 2005; 191(10):1631-8. DOI: 10.1086/429832. View

17.

Florens L, Washburn M, Raine J, Anthony R, Grainger M, Haynes J . A proteomic view of the Plasmodium falciparum life cycle. Nature. 2002; 419(6906):520-6. DOI: 10.1038/nature01107. View

18.

Doolan D, Mu Y, Unal B, Sundaresh S, Hirst S, Valdez C . Profiling humoral immune responses to P. falciparum infection with protein microarrays. Proteomics. 2008; 8(22):4680-94. PMC: 3021802. DOI: 10.1002/pmic.200800194. View

19.

Hill A, Allsopp C, Kwiatkowski D, Anstey N, Twumasi P, Rowe P . Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991; 352(6336):595-600. DOI: 10.1038/352595a0. View

20.

Hiller N, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano C . A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science. 2004; 306(5703):1934-7. DOI: 10.1126/science.1102737. View