Interactions oe host immune responses, iron status and genetic backgrounds in the pathogenesis of malarial anaemia in children
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Date
2008
Authors
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Publisher
Sokoine University of Agriculture
Abstract
In search for pathophysiological mechanisms of malarial anaemia, this study
investigated several serum soluble factors (cytokines, growth factors, iron
markers) and mechanisms (red cell aging, complement regulation, genetic red cell
disorders) that may explain why some children with malaria develop anaemia.
Among anaemic malaria patients, children with inappropriate reticulocyte
responses were compared to those with normal reticulocyte responses for the
differences in serum soluble factor levels. Serum soluble factors were analyzed by
multiplex bead-based platform with custom sandwich or competitive assay kits.
Children with inappropriate reticulocyte responses had higher IL-1, IL-6, TNI-'-a.
IL-10 and TNF-a/IL-10 ratio, and lower erythropoietin levels. In multivariate
logistic regression analyses, only erythropoietin remained significantly associated
and inversely related to poor reticulocyte response suggesting that erythropoietin
influences rcticulocytosis during malaria. RBC membrane surface molecules were
measured by cytolluorometry and analyzed for their relationship with cytokine
levels. RBC age and anaemia during acute malaria. Phosphatidylserine. IgG,
CD35. CD55 and CD59 levels were not associated with cytokine levels, whereas
TNF-a/IL-10 ratio associated positively with CD59 only. Loss of CD55 and CD59
occurs during erythrocyte ageing but this effect docs not explain the changes
occurring during malarial anaemia. CD55 levels were significantly lower in
anaemic children and correlated positively with haemoglobin level, suggesting
that the loss of CD55 may contribute to malarial anaemia. Immune responses to
P.falciparum malaria in children with different genetic backgrounds were studied
before and during first malaria episodes. Haemoglobin levels did not varyiii
according to the genetic backgrounds before malaria infection. Parasitemia.
haemoglobin and cytokine levels (IL-1. IL-6. IFN-y and IL-5) were significantly
higher in age-matched children with normal haemoglobin than sickle cell carriers
during malaria. Levels of TNF-a and ferritin varied on the basis of thalassemia
status, and none of the serum soluble factors levels varied on the basis of G6PD
genotypes. The results suggest that genetic red cell disorders vary in their effects
to modulate immune response and these variations may be influencing disease
outcomes. From these data it is concluded that several host factors interact to
contribute to acute malarial anaemia including EPO response, CrP levels on RBC
and genetic backgrounds.
Description
PhD Thesis
Keywords
Genetic backgrounds, Malarial Anaemia, Iron status, Host immune responses