C1 Inhibitor, C3 Activator, IgG, IgA, and IgM Titers in Nigerian Sickle Cell Disease Patients with Plasmodium falciparum

Abstract

<b>Background</b>: Sickle cell disease (HbSS) is a major health problem in Nigeria and ma-laria has been implicated as a leading cause of morbidity/mortality in sickle cell disease patients. Few reasons were put forward to explain the observed morbidity/mortality of HbSS subjects due to Plasmodium falciparum (P. falciparum) malaria. <br/><b>Objectives</b>: To determine the level of immunoglobulin classes (IgM, IgA, and IgG) and regulators of complement system (C1 inhibitor and C3 activator) in Nigerian HbSS patients with and without P. falciparum parasitemia. <br/><b>Methods</b>: A total of 64 subjects were considered, including 10 HbSS genotypic subjects with P. falciparum parasitemia (HbSS+PfM), 18 HbAA genotypic subjects with P. falciparum parasitemia (HbAA+PfM), 20 HbSS without P. falciparum parasitemia (HbSS-PfM), and 16 HbAA genotypic subjects with-out P. falciparum parasitemia (HbAA-PfM). IgM, IgA, IgG, C1 inhibitor, and C3 acti-vator titers were quantified by single radial immunodiffusion method. <br/><b>Results</b>: The mean levels of IgG in HbSS+PfM (2373.90±1772.81mg/dl) and HbAA+PfM (1868.80±0.00mg/dl) were significantly higher compared with HbSS-PfM (644.55±171.15mg/dl) or HbAA-PfM (659.75±158.01mg/dl) patients. HbAA-PfM sub-jects had the lowest level of IgM (67.27±63.7mg/dl), though no significant difference was observed comparing mean levels of IgM between the four groups. IgA titer was significantly higher in HbSS-PfM patients (249.00±94.8mg/dl) compared with HbAA-PfM (p<0.05), HbAA+PfM (p<0.05), or HbSS+PfM (p<0.05). The mean values of C1 inhibitor were lower in HbSS+PfM and HbAA+PfM compared with HbSS-PfM or HbAA-PfM. However, HbAA+PfM had a significantly lower value of C1 inhibitor compared with HbAA-PfM (p<0.01). C3 activator was highest in HbSS-PfM (17.10±7.35mg/dl) and was significantly higher compared with HbSS+PfM (p<0.05). <br/><b>Conclusion</b>: Increased C1 inhibitor and decreased C3 activator in HbSS+PfM com-pared with HbAA+PfM shows that deranged regulation of complement factors may be responsible for increased susceptibility of HbSS to P. falciparum malaria.