Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya

Abstract

Aims: Malaria infection leads to the formation of circulating immune complexes (CICs) which have been implicated in the pathogenesis of complicated malaria which includes severe malarial anemia. Children with sickle cell trait (HbAS) are less predisposed to getting severe manifestations of malaria. We carried out a study to determine the competence of the red blood cells (RBCs) of children with HbAS to bind immune complexes (ICs) and compared this with normal hemoglobin (HbAA). Methods: Children (aged 0-192 months) were enrolled in a nested case controlled study conducted in Kombewa Division, Kisumu West District, Kenya. 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 69 HbAA of similar age. The children were further categorized into three cohorts (0-12, 13-48 and 49-192 months). Immune complex binding capacity (ICBC) was quantified using a FACScan flow cytometer under normal and reduced oxygen saturation. Results: The mean immune complex binding capacity for the HbAS cells was significantly higher than that of HbAA cells (P=0.0191) under normal oxygen saturation or under reduced oxygen saturation (P=0.0050). When a matching variable (UNIANOVA) was done to control for age, gender, the presence or absence of malaria parasitaemia, the binding capacity was again significantly higher for the HbAS than for HbAA under normal oxygen saturation (P=0.025) and under reduced oxygen saturation (P=0.003). The binding capacity was lowest in the 7-12 months age group for both HbAS and HbAA; however, the overall picture showed that HbAS individuals had higher immune complex binding capacity than HbAA in all the age cohorts. Conclusion: These results demonstrate that the protection afforded by HbAS against severe manifestations of malaria may be partly due to higher immune complex binding capacity of the HbAS compared to the HbAA cells. This high binding capacity may lead to the mopping up of ICs formed during malaria attacks and therefore protect these cells from deposition and subsequent destruction.