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Research Article Open access CC BY 3.0

Sickle Cell Trait (HbAS) is Associated with Increased Expression of Erythrocyte Complement Regulatory Proteins CR1 and CD55 Levels in Children

Walter Otieno, Benson B. A. Estambale, Michael M. Odera, Stacey M. O. Gondi, Joash R. Aluoch, José A. Stoute

International Journal of TROPICAL DISEASE & Health · pp. 133–147 · Published 2 Apr 2013

10.9734/IJTDH/2013/2948

Abstract

Aims: Erythrocyte complement regulatory proteins, complement receptor 1 (CR1) and decay accelerating factor (CD55) protect red blood cells (RBCs) from complement mediated damage by controlling complement activation cascade and potentially protect RBCs from complement mediated damage that may occur when immune complexes are formed following malaria infection. Given the important role of RBCs in regulation of complement activation, we considered the competence of sickle cell trait RBCs in these functions. Methods: Children (age 0-192 months; n=116) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu west District between October and December 2004. Based on hemoglobin (Hb) type, children were stratified into those with HbAS (n=47) and HbAA (n=69). The 47 HbAS individuals were matched to the 69 HbAA individuals of similar age (± 2 months or ± 24 months for those below or more than 192 months, respectively) at a ratio of 1:1 or 1:2. Circulating CR1 levels and CD levels were quantified using a FACScan cytometer under normal and reduced oxygen saturation. Results: The mean CR1 copy numbers per RBC was comparable in the two groups. However, between the ages of 49-192 months, the mean CR1 copy numbers per erythrocyte was significantly higher in children who had HbAS compared to those with HbAA (P=0.0332). The mean CD55 levels were comparable between the two groups but after deoxygenation, the mean CD levels in RBCs of individuals with HbAS was significantly higher than in the HbAA (P=0.011). Conclusion: The mean CR1 and CD55 copy numbers per RBC were comparable between the two groups under normal and reduced oxygen saturation. Beyond the age of 49 months, the CR1 copy numbers was higher in the HbAS compared to HbAA and this was also true for CD55 levels under deoxygenated conditions. Taken together, these results demonstrate that in the younger age groups, the protection afforded by HbAS against severe manifestations of malaria may be due to other factors other than complement regulatory proteins but beyond the age of 49 months, this protection may be partly due to the high CR1 copy numbers in the HbAS individuals.

Plasmodium falciparum malaria CR1 CD55 sickle cell trait.

References (40)

  1. 1 Common West African HLA antigens are associated with protection from severe malaria [DOI]
  2. 2 Inherited haemoglobin disorders: an increasing global health problem.
  3. 3 Protective effects of the sickle cell gene against malaria morbidity and mortality [DOI]
  4. 4 Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria [DOI]
  5. 5 P. falciparum rosetting mediated by a parasite-variant erythrocyte membrane protein and complement-receptor 1 [DOI]
  6. 6 Invasion of Erythrocytes by Malaria Merozoites [DOI]
  7. 7 Sickle Cell Trait and the Risk ofPlasmodium falciparumMalaria and Other Childhood Diseases [DOI]
  8. 8 Cellular mechanism for the protective effect of haemoglobin S against P. falciparum malaria [DOI]
  9. 9 An Immune Basis for Malaria Protection by the Sickle Cell Trait [DOI]
  10. 10 Human red blood cell polymorphisms and malaria [DOI]
  11. 11 Malaria-a neglected disease? [DOI]
  12. 12 Red cell surface changes and erythrophagocytosis in children with severe Plasmodium falciparum anemia [DOI]
  13. 13 Natural protection against severe Plasmodium falciparum malaria due to impaired rosette formation [DOI]
  14. 14 Loss of Red Blood Cell–Complement Regulatory Proteins and Increased Levels of Circulating Immune Complexes Are Associated with Severe Malarial Anemia [DOI]
  15. 15 Population Dynamics of Malaria Vectors in Western Kenya Highlands [DOI]
  16. 16 Haemoglobin C and S Role in Acquired Immunity against Plasmodium falciparum Malaria [DOI]
  17. 17 Higher resistance to Plasmodium falciparum infection in patients with homozygous sickle cell disease in western Kenya [DOI]
  18. 18 CR1 density polymorphism on erythrocytes of falciparum malaria patients in Thailand. [DOI]
  19. 19 Age‐Related Changes in Red Blood Cell Complement Regulatory Proteins and Susceptibility to Severe Malaria [DOI]
  20. 20 Complement decay accelerating factor (DAF)/CD55 in cancer [DOI]
  21. 21 Complement activation in experimental human malaria infection [DOI]
  22. 22 Reduced Immune Complex Binding Capacity and Increased Complement Susceptibility of Red Cells from Children with Severe Malaria-Associated Anemia [DOI]
  23. 23 Common genetic disorders of the red cell and the ‘malaria hypothesis’ [DOI]
  24. 24 Genetic epidemiology of the βs gene [DOI]
  25. 25 Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria [DOI]
  26. 26 Complement-regulatory proteins in severe malaria: too little or too much of a good thing? [DOI]
  27. 27 The interaction between sickle haemoglobin and the malarial parasite Plasmodium falciparum [DOI]
  28. 28 IMMUNE COMPLEX LEVELS IN CHILDREN WITH SEVERE PLASMODIUM FALCIPARUM MALARIA [DOI]
  29. 29 Autoantibodies, immunoglobulins, complement and circulating immune complexes in acute malaria.
  30. 30 Owuor BO, Odhiambo CO, Otieno WO, Adhiambo C, Makawiti DW, Stoute JA.Reduced immune complex binding capacity and increased complement susceptibility of red cells from children with severe malaria-associated anemia.Mol Med. 2008 Mar-Apr;14(3-4):89-97
  31. 31 Association between Sickle Cell Trait and Low Density Parasitaemia in a P. falciparum Malaria Holoendemic Region of Western Kenya [DOI]
  32. 32 Thalassaemia in Vanuatu, South‐West Pacific: frequency and haematological phenotypes of young children [DOI]
  33. 33 A simple method for accurate quantification of complement receptor 1 on erythrocytes preserved by fixing or freezing [DOI]
  34. 34 Hb Kenya among Luo Adults and Young Children in Malaria Holoendemic Western Kenya: Screened by High Performance Liquid Chromatography and Confirmed By Polymerase Chain Reaction [DOI]
  35. 35 Cerebral Malaria in Mice: Demonstration of Cytoadherence of Infected Red Blood Cells and Microrheologic Correlates [DOI]
  36. 36 Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals [DOI]
  37. 37 Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya [DOI]
  38. 38 Quantitative determination of antibody binding capacity (ABC) by flow cytometry.
  39. 39 The presence of sickle cells in the peripheral blood film. Specificity and sensitivity of diagnosis of homozygous sickle cell disease in Kenya.
  40. 40 [Morbidity and severity of malaria attacks in carriers of sickle-cell trait].

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No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes

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