RP-Department of Pre-clinical Sciences

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Browsing RP-Department of Pre-clinical Sciences by Author "Stoute, J. A."

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    Distinct Pattern of Class and Subclass Antibodies in Immune Complexes of Children with Cerebral Malaria and Severe Malarial Anaemia.
    (Parasite Immunology Journal, 2008) Mibei, Erick Kipsang; Otieno, W. O.; Orago, A. S.; Stoute, J. A.
    Plasmodium falciparum infection can lead to deadly complications such as severe malaria-associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrollment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4-containing IC levels and increased risk of SMA (OR = 3.11, 95% CI 1.01-9.56, P = 0.05). Total IgG ICs (OR = 2.84, 95% CI 1.08-7.46, P = 0.03) and IgE-containing ICs (OR = 6.82, OR 1.88-24.73, P < or = 0.01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.
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    Immune Complex Levels in Children with Severe Plasmodium Falciparum Malaria.
    (The American Society of Tropical Medicine, 2000-05) Mibei, Erick Kipsang; Orago, A. S.; Stoute, J. A.
    Malaria infection leads to the formation of circulating immune complexes. However, it is unclear whether these complexes play a role in the pathogenesis of complicated Plasmodium falciparum malaria. This study aimed at determining if there are differences in the levels of immune complexes between children with severe malaria-associated anemia and cerebral malaria and between each of these two groups and their respective uncomplicated symptomatic malaria or healthy asymptomatic controls. Children with severe malaria-associated anemia and cerebral malaria had significantly higher immune complex levels than their respective controls, but there were no significant differences in the levels between the two severe malaria groups. In addition, there was an inverse relationship between the hemoglobin levels and immune complex levels in the severe anemia controls, suggesting that immune complexes may contribute to erythrocyte destruction in these children. These results suggest that immune complex levels alone cannot account for the differences in the distinct clinical presentation between severe malaria-associated anemia and cerebral malaria.
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    The levels of CD16/Fc gamma receptor IIIA on CD14+ CD16+ monocytes are higher in children with severe Plasmodium falciparum anemia than in children with cerebral or uncomplicated malaria.
    (PubMed, 2010) Ogonda, Frederick L. A.; Orago, A. S.; Otieno, M.; Adhiambo, C.; Otieno, W.; Stoute, J. A.
    Fc gamma receptor IIIA (CD16/Fc gamma RIIIA) on monocytes/macrophages may play an important role in the pathogenesis of severe malarial anemia (SMA) by promoting phagocytosis of IgG-coated uninfected red cells and by allowing the production of tumor necrosis factor alpha (TNF-alpha) upon cross-linking by immune complexes (ICs). However, not much is known about the differential expression of this receptor on monocytes of children with severe malaria and uncomplicated malaria. Therefore, we investigated the expression of CD16/Fc gamma RIIIA on monocytes of children with SMA, cerebral malaria (CM), and their age-matched uncomplicated malaria controls by flow cytometry. Since CD14 low (CD14(+)) monocytes are considered more mature and macrophage-like than CD14 high (CD14(++)) monocytes, we also compared the level of expression of CD16/Fc gamma RIIIA according to the CD14 level and studied the relationship between CD16/Fc gamma RIIIA expression and intracellular TNF-alpha production upon stimulation by ICs. CD16/Fc gamma RIIIA expression was the highest overall on CD14(+) CD16(+) monocytes of children with SMA at enrollment. At convalescence, SMA children were the only ones to show a significant decline in the same parameter. In contrast, there were no significant differences among groups in the expression of CD16/Fc gamma RIIIA on CD14(++) CD16(+) monocytes. A greater percentage of CD14(+) CD16(+) monocytes produced TNF-alpha upon stimulation than any other monocyte subset, and the amount of intracellular TNF-alpha correlated positively with CD16/Fc gamma RIIIA expression. Furthermore, there was an inverse correlation between hemoglobin levels and CD16/Fc gamma RIIIA expression in children with SMA and their controls. These data suggest that monocytes of children with SMA respond differently to Plasmodium falciparum infection by overexpressing CD16/Fc gamma RIIIA as they mature, which could enhance erythrophagocytosis and TNF-alpha production.