Volume 69, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Malaria continues to claim the lives of more children worldwide than any other infectious disease, and improved understanding of disease immunology is a priority for the development of new therapeutic and vaccination strategies. FcγRIIa (CD32) contains a polymorphic variant (H/R131) that has been associated with variability in susceptibility to both bacterial diseases and parasitemia. We investigated the role of this polymorphism in West Africans with mild and severe malarial disease. The HH131 genotype was significantly associated with susceptibility to severe malaria ( = 0.03, odds ratio = 1.40, 95% confidence interval = 1.02–1.91). In contrast to studies of parasitemia, the presence of the R131 allele, rather than the RR131 genotype, appeared to be the important factor in protection from disease. This is the first evidence for an association between CD32 polymorphism and severe malaria and provides an example of balancing selective pressures from different infectious diseases operating at the same genetic locus.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Warmerdam PA, van de Winkel JG, Vlug A, Westerdaal NA, Capel PJ, 1991. A single amino acid in the second Ig-like domain of the human Fc gamma receptor II is critical for human IgG2 binding. J Immunol 147 : 1338–1343. [Google Scholar]
  2. Stein MP, Edberg JC, Kimberly RP, Mangan EK, Bharadwaj D, Mold C, Du Clos TW, 2000. C-reactive protein binding to FcgammaRIIa on human monocytes and neutrophils is allele-specific. J Clin Invest 105 : 369–376. [Google Scholar]
  3. Platonov AE, Shipulin GA, Vershinina IV, Dankert J, van de Winkel JG, Kuijper EJ, 1998. Association of human Fc gamma RIIa (CD32) polymorphism with susceptibility to and severity of meningococcal disease. Clin Infect Dis 27 : 746–750. [Google Scholar]
  4. Bredius RG, Derkx BH, Fijen CA, de Wit TP, de Haas M, Weening RS, van Winkel JG, Out TA, 1994. Fcγ receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. J Infect Dis 170 : 848–853. [Google Scholar]
  5. Yee AM, Phan HM, Zuniga R, Salmon JE, Musher DM, 2000. Association between FcgammaRIIa-R131 allotype and bacteremic pneumococcal pneumonia. Clin Infect Dis 30 : 25–28. [Google Scholar]
  6. Pied S, Nussler A, Pontent M, Miltgen F, Matile H, Lambert PH, Mazier D, 1989. C-reactive protein protects against preerythrocytic stages of malaria. Infect Immun 57 : 278–282. [Google Scholar]
  7. Druilhe P, Sabchareon A, Bouharoun-Tayoun H, Oeuvray C, Perignon JL, 1997. In vivo veritas: lessons from immunoglobulin-transfer experiments in malaria patients. Ann Trop Med Parasitol 91 : S37–S53. [Google Scholar]
  8. Bouharoun-Tayoun H, Druilhe P, 1992. Plasmodium falciparum malaria: evidence for an isotype imbalance which may be responsible for delayed acquisition of protective immunity. Infect Immun 60 : 1473–1481. [Google Scholar]
  9. Braga EM, Barros RM, Reis TA, Fontes CJ, Morais CG, Martins MS, Krettli AU, 2002. Association of the IgG response to Plasmodium falciparum merozoite protein (C-terminal 19 kD) with clinical immunity to malaria in the Brazilian Amazon region. Am J Trop Med Hyg 66 : 461–466. [Google Scholar]
  10. Taylor RR, Allen SJ, Greenwood BM, Riley EM, 1998. IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. Am J Trop Med Hyg 58 : 406–413. [Google Scholar]
  11. Oeuvray C, Theisen M, Rogier C, Trape JF, Jepsen S, Druilhe P, 2000. Cytophilic immunoglobulin responses to Plasmodium falciparum glutamate-rich protein are correlated with protection against clinical malaria in Dielmo, Senegal. Infect Immun 68 : 2617–2620. [Google Scholar]
  12. Aucan C, Traore Y, Tall F, Nacro B, Traore-Leroux T, Fumoux F, Rihet P, 2000. High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria. Infect Immun 68 : 1252–1258. [Google Scholar]
  13. Shi YP, Nahlen BL, Kariuki S, Urdahl KB, McElroy PD, Roberts JM, Lal AA, 2001. Fcgamma receptor IIa (CD32) polymorphism is associated with protection of infants against high-density Plasmodium falciparum infection. VII. Asembo Bay Cohort Project. J Infect Dis 184 : 107–111. [Google Scholar]
  14. Omi K, Ohashi J, Patarapotikul J, Hananantachai H, Naka I, Looareesuwan S, Tokunaga K, 2002. Fcgamma receptor IIA and IIIB polymorphisms are associated with susceptibility to cerebral malaria. Parasitol Int 51 : 361–366. [Google Scholar]
  15. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM, 1991. Common west African HLA antigens are associated with protection from severe malaria. Nature 352 : 595–600. [Google Scholar]
  16. Jiang XM, Arepally G, Poncz M, McKenzie SE, 1996. Rapid detection of the Fc gamma RIIA-H/R 131 ligand-binding polymorphism using an allele-specific restriction enzyme digestion (ASRED). J Immunol Methods 199 : 55–59. [Google Scholar]
  17. Bredius RG, Derkx BH, Fijen CA, de Wit TP, de Haas M, Weening RS, van de Winkel JG, Out TA, 1994. Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children. J Infect Dis 170 : 848–853. [Google Scholar]
  18. Bredius RG, de Vries CE, Troelstra A, van Alphen L, Weening RS, van de Winkel JG, Out TA, 1993. Phagocytosis of Staphylococcus aureus and Haemophilus influenzae type B opsonized with polyclonal human IgG1 and IgG2 antibodies. Functional hFc gamma RIIa polymorphism to IgG2. J Immunol 151 : 1463–1472. [Google Scholar]
  19. Greenwood B, 1999. Manson Lecture. Meningococcal meningitis in Africa. Trans R Soc Trop Med Hyg 93 : 341–353. [Google Scholar]
  20. Goetghebuer T, West TE, Wermenbol V, Cadbury AL, Milligan P, Lloyd-Evans N, Adegbola RA, Mulholland EK, Greenwood BM, Weber MW, 2000. Outcome of meningitis caused by Streptococcus pneumoniae and Haemophilus influenzae type b in children in The Gambia. Trop Med Int Health 5: 207–213. [Google Scholar]
  21. Rascu A, Repp R, Westerdaal NA, Kalden JR, van de Winkel JG, 1997. Clinical relevance of Fc gamma receptor polymorphisms. Ann N Y Acad Sci 815 : 282–295. [Google Scholar]

Data & Media loading...

  • Received : 30 Apr 2003
  • Accepted : 09 Jul 2003

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error