Increased Complement Deposition on Red Blood Cells in Children with Sickle Cell Trait

Aims: Immune-mediated mechanism, such as deposition of complement (C3b) on erythrocytes leading to enhanced receptor-mediated uptake by macrophages has been proposed to contribute partly to the destruction of non-infected cells leading to anaemia. The extent of complement deposition on RBC (red blood cells) may therefore influence an individual's resistance or susceptibility to severe malarial anaemia. Our objective was to see if RBC of sickle cell trait individuals have increased susceptibility to deposition of complement in vivo. Under oxygenated and deoxygenated conditions, cytofluorometry was used to determine susceptibility of RBC from individuals with normal haemoglobin and those with heterozygous sickle cell trait to complement deposition.
Methods: Children aged 0-192 months (n=116) were enrolled in the nested case controlled study and were stratified into 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. We measured the red cell C3b by flow cytometry under normal and reduced oxygen saturation. Individuals who were positive for malaria were treated and blood was collected when they were free of parasitemia. Analysis of variance was used to identify independent variables associated with the complement C3b positive red cells and Hb level.
Results: The mean complement C3b-positive cells for the HbAS was significantly higher than HbAA (P=0.0191). This was also true when this was repeated under deoxygenated conditions (P=0.00065). When the study volunteers were grouped by age cohorts into 0-12, 13-48 and 49-192 months, it was noted that generally; the mean complement C3b positive red cells was higher in the HbAS compared to HbAA but was not statistically significant. Under deoxygenated conditions, the trend was the same. However, between the ages of 49-192 months, the difference was statistically significant.
Conclusion: Increased complement C3b deposition on red cells of HbAS cells may predispose the HbAS individuals to increased RBC destruction and therefore protection from severe manifestations of malaria.