1921
Volume 71, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

We used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant surface antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1α (DBL-1α ) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the erythrocyte membrane protein 1 (PfEMP1) DBL-1α domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens’ history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2004.71.2.0700179
2004-08-01
2019-03-25
Loading full text...

Full text loading...

/deliver/fulltext/14761645/71/2/0700179.html?itemId=/content/journals/10.4269/ajtmh.2004.71.2.0700179&mimeType=html&fmt=ahah

References

  1. Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh K, Newbold CI, 1992. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357: 689–692. [Google Scholar]
  2. Brannan LR, Turner CM, Phillips RS, 1994. Malaria parasites undergo antigenic variation at high rates in vivo. Proc R Soc Lond B Biol Sci 256: 71–75. [Google Scholar]
  3. Marsh K, Otoo L, Hayes RJ, Carson DC, Greenwood BM, 1989. Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection. Trans R Soc Trop Med Hyg 83: 293–303. [Google Scholar]
  4. Bull PC, Lowe BS, Kortok M, Molyneux CS, Newbold CI, Marsh K, 1998. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nat Med 4: 358–360. [Google Scholar]
  5. Tebo AE, Kremsner PG, Piper KP, Luty AJ, 2002. Low antibody responses to variant surface antigens of Plasmodium falciparum are associated with severe malaria and increased susceptibility to malaria attacks in Gabonese children. Am J Trop Med Hyg 67: 597–603. [Google Scholar]
  6. Tebo AE, Kremsner PG, Luty AJ, 2002. Fcgamma receptor-mediated phagocytosis of Plasmodium falciparum-infected erythrocytes in vitro. Clin Exp Immunol 130: 300–306. [Google Scholar]
  7. Newbold CI, Craig AG, Kyes S, Berendt AR, Snow RW, Peshu N, Marsh K, 1997. PfEMP1, polymorphism and pathogenesis. Ann Trop Med Parasitol 91: 551–557. [Google Scholar]
  8. Berendt AR, Ferguson DJ, Gardner J, Turner G, Rowe A, McCormick C, Roberts D, Craig A, Pinches R, Elford BC, New-bold CI, 1994. Molecular mechanisms of sequestration in malaria. Parasitology 108: S19–S28. [Google Scholar]
  9. Su XZ, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE, 1995. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82: 89–100. [Google Scholar]
  10. Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ, 1995. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82: 77–87. [Google Scholar]
  11. Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH, 1995. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82: 101–110. [Google Scholar]
  12. Smith JD, Craig AG, Kriek N, Hudson-Taylor D, Kyes S, Fagen T, Pinches R, Baruch DI, Newbold CI, Miller LH, 2000. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc Natl Acad Sci USA 97: 1766–1771. [Google Scholar]
  13. Handunnetti SM, David PH, Perera KL, Mendis KN, 1989. Uninfected erythrocytes form “rosettes” around Plasmodium falciparum infected erythrocytes. Am J Trop Med Hyg 40: 115–118. [Google Scholar]
  14. Udomsangpetch R, Wahlin B, Carlson J, Berzins K, Torii M, Aikawa M, Perlmann P, Wahlgren M, 1989. Plasmodium falciparum-infected erythrocytes form spontaneous erythrocyte rosettes. J Exp Med 169: 1835–1840. [Google Scholar]
  15. Vogt AM, Barragan A, Chen Q, Kironde F, Spillmann D, Wahlgren M, 2003. Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1. Blood 101: 2405–2411. [Google Scholar]
  16. Chen Q, Barragan A, Fernandez V, Sundstrom A, Schlichtherle M, Sahlen A, Carlson J, Datta S, Wahlgren M, 1998. Identification of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) as the rosetting ligand of the malaria parasite P. falciparum. J Exp Med 187: 15–23. [Google Scholar]
  17. Oguariri RM, Borrmann S, Klinkert MQ, Kremsner PG, Kun JF, 2001. High prevalence of human antibodies to recombinant Duffy binding-like alpha domains of the Plasmodium falciparum-infected erythrocyte membrane protein 1 in semi-immune adults compared to that in nonimmune children. Infect Immun 69: 7603–7609. [Google Scholar]
  18. Kyes SA, Rowe JA, Kriek N, Newbold CI, 1999. Rifins: a second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc Natl Acad Sci USA 96: 9333–9338. [Google Scholar]
  19. Fernandez V, Hommel M, Chen Q, Hagblom P, Wahlgren M, 1999. Small, clonally variant antigens expressed on the surface of the Plasmodium falciparum-infected erythrocyte are encoded by the rif gene family and are the target of human immune responses. J Exp Med 190: 1393–1404. [Google Scholar]
  20. Kyes S, Pinches R, Newbold C, 2000. A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum. Mol Biochem Parasitol 105: 311–315. [Google Scholar]
  21. Abdel-Latif MS, Khattab A, Lindenthal C, Kremsner PG, Klinkert MQ, 2002. Recognition of variant rifin antigens by human antibodies induced during natural Plasmodium falciparum infections. Infect Immun 70: 7013–7021. [Google Scholar]
  22. Abdel-Latif MS, Dietz K, Issifou S, Kremsner PG, Klinkert MQ, 2003. Antibodies to Plasmodium falciparum rifin proteins are associated with rapid parasite clearance and asymptomatic infections. Infect Immun 71: 6229–6233. [Google Scholar]
  23. Wildling E, Winkler S, Kremsner PG, Brandts C, Jenne L, Wernsdorfer WH, 1995. Malaria epidemiology in the province of Moyen Ogoov, Gabon. Trop Med Parasitol 46: 77–82. [Google Scholar]
  24. Sylla EHK, Kun JFJ, Kremsner PG, 2000. Mosquito distribution and entomological inoculation rates in three malaria-endemic areas in Gabon. Trans R Soc Trop Med Hyg 94: 652–656. [Google Scholar]
  25. Kun JF, Mordmuller B, Lell B, Lehman LG, Luckner D, Kremsner PG, 1998. Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 351: 265–266. [Google Scholar]
  26. Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG, 1998. Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg 92: 110–114. [Google Scholar]
  27. Warrell D, Molyneux M, Beales P, 1990. Severe and complicated malaria. Trans R Soc Trop Med Hyg 84 (Suppl 2): 1–65. [Google Scholar]
  28. Trager W, Jensen JB, 1977. Cultivation of erythrocytic stages. Bull World Health Organ 55: 363–365. [Google Scholar]
  29. Piper KP, Roberts DJ, Day KP, 1999. Plasmodium falciparum: analysis of the antibody specificity to the surface of the trophozoite-infected erythrocyte. Exp Parasitol 91: 161–169. [Google Scholar]
  30. Luty AJ, Ulbert S, Lell B, Lehman L, Schmidt-Ott R, Luckner D, Greve B, Matousek P, Schmid D, Herbich K, Dubois B, Deloron P, Kremsner PG, 2000. 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 62: 566–572. [Google Scholar]
  31. Marsh K, 1992. Malaria-a neglected disease? Parasitology 104: S53–S69. [Google Scholar]
  32. Gupta S, Snow RW, Donnelly CA, Marsh K, Newbold C, 1999. Immunity to non-cerebral severe malaria is acquired after one or two infections. Nat Med 5: 340–343. [Google Scholar]
  33. Chattopadhyay R, Sharma A, Srivastava VK, Pati SS, Sharma SK, Das BS, Chitnis CE, 2003. Plasmodium falciparum infection elicits both variant-specific and cross-reactive antibodies against variant surface antigens. Infect Immun 71: 597–604. [Google Scholar]
  34. Newbold CI, Pinches R, Roberts DJ, Marsh K, 1992. Plasmodium falciparum: the human agglutinating antibody response to the infected red cell surface is predominantly variant specific. Exp Parasitol 75: 281–292. [Google Scholar]
  35. Gamain B, Miller LH, Baruch DI, 2001. The surface variant antigens of Plasmodium falciparum contain cross-reactive epitopes. Proc Natl Acad Sci USA 98: 2664–2669. [Google Scholar]
  36. Cabrera G, Yone C, Tebo AE, van Aaken J, Lell B, Kremsner PG, Luty AJF, 2004. IgG isotype responses to variant surface antigens of Plasmodium falciparum in healthy Gabonese adults and in children during and after successive malaria attacks. Infect Immun 72: 284–294. [Google Scholar]
  37. Beeson JG, Mann EJ, Elliott SR, Lema VM, Tadesse E, Molyneux ME, Brown GV, Rogerson SJ, 2004. Antibodies to variant surface antigens of Plasmodium falciparum-infected erythrocytes and adhesion-inhibitory antibodies are associated with placental malaria and have overlapping and distinct targets. J Infect Dis 189: 540–551. [Google Scholar]
  38. Nielsen MA, Staalsoe T, Kurtzhals JA, Goka BQ, Dodoo D, Alifrangis M, Theander TG, Akanmori BD, Hviid L, 2002. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity. J Immunol 168: 3444–3450. [Google Scholar]
  39. Ofori MF, Dodoo D, Staalsoe T, Kurtzhals JA, Koram K, Theander TG, Akanmori BD, Hviid L, 2002. Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens. Infect Immun 70: 2982–2988. [Google Scholar]
  40. Bull PC, Lowe BS, Kaleli N, Njuga F, Kortok M, Ross A, Ndungu F, Snow RW, Marsh K, 2002. Plasmodium falciparum infections are associated with agglutinating antibodies to parasite-infected erythrocyte surface antigens among healthy Kenyan children. J Infect Dis 185: 1688–1691. [Google Scholar]
  41. Baruch DI, Gamain B, Miller LH, 2003. DNA immunization with the cysteine-rich interdomain region 1 of the Plasmodium falciparum variant antigen elicits limited cross-reactive antibody responses. Infect Immun 71: 4536–4543. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2004.71.2.0700179
Loading
/content/journals/10.4269/ajtmh.2004.71.2.0700179
Loading

Data & Media loading...

  • Received : 27 Oct 2003
  • Accepted : 11 Feb 2004

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