Early and extensive CD55 loss from red blood cells supports a causal role in malarial anaemia

BACKGROUND\ud \ud Levels of complement regulatory proteins (CrP) on the surface of red blood cells (RBC) decrease during severe malarial anaemia and as part of cell ageing process. It remains unclear whether CrP changes seen during malaria contribute to the development of anaemia, or result from an altered RBC age distribution due to suppressive effects of malaria on erythropoiesis.\ud \ud METHODS\ud \ud A cross sectional study was conducted in the north-east coast of Tanzania to investigate whether the changes in glycosylphosphatidylinositol (GPI)-anchored complement regulatory proteins (CD55 and CD59) contributes to malaria anaemia. Blood samples were collected from a cohort of children under intensive surveillance for Plasmodium falciparum parasitaemia and illness. Levels of CD55 and CD59 were measured by flow cytometer and compared between anaemic (8.08 g/dl) and non- anaemic children (11.42 g/dl).\ud \ud RESULTS\ud \ud Levels of CD55 and CD59 decreased with increased RBC age. CD55 levels were lower in anaemic children and the difference was seen in RBC of all ages. Levels of CD59 were lower in anaemic children, but these differences were not significant. CD55, but not CD59, levels correlated positively with the level of haemoglobin in anaemic children.\ud \ud CONCLUSION\ud \ud The extent of CD55 loss from RBC of all ages early in the course of malarial anaemia and the correlation of CD55 with haemoglobin levels support the hypothesis that CD55 may play a causal role in this disorder

No Evidence that Knops Blood Group Polymorphisms Affect Complement Receptor 1 Clustering on Erythrocytes

Clustering of Complement Receptor 1 (CR1) in the erythrocyte membrane is important for immune-complex transfer and clearance. CR1 contains the Knops blood group antigens, including the antithetical pairs Swain-Langley 1 and 2 (Sl1 and Sl2) and McCoy a and b (McCa and McCb), whose functional effects are unknown. We tested the hypothesis that the Sl and McC polymorphisms might influence CR1 clustering on erythrocyte membranes. Blood samples from 125 healthy Kenyan children were analysed by immunofluorescence and confocal microscopy to determine CR1 cluster number and volume. In agreement with previous reports, CR1 cluster number and volume were positively associated with CR1 copy number (mean number of CR1 molecules per erythrocyte). Individuals with the McCb/McCb genotype had more clusters per cell than McCa/McCa individuals. However, this association was lost when the strong effect of CR1 copy number was included in the model. No association was observed between Sl genotype, sickle cell genotype, α+thalassaemia genotype, gender or age and CR1 cluster number or volume. Therefore, after correction for CR1 copy number, the Sl and McCoy polymorphisms did not influence erythrocyte CR1 clustering, and the effects of the Knops polymorphisms on CR1 function remains unknown

Increased deposition of C3b on red cells with low CR1 and CD55 in a malaria-endemic region of western Kenya: Implications for the development of severe anemia

<p>Abstract</p> <p>Background</p> <p>Severe anemia due to <it>Plasmodium falciparum </it>malaria is a major cause of mortality among young children in western Kenya. The factors that lead to the age-specific incidence of this anemia are unknown. Previous studies have shown an age-related expression of red cell complement regulatory proteins, which protect erythrocytes from autologous complement attack and destruction. Our primary objective was to determine whether in a malaria-endemic area red cells with low levels of complement regulatory proteins are at increased risk for complement (C3b) deposition <it>in vivo</it>. Secondarily, we studied the relationship between red cell complement regulatory protein levels and hemoglobin levels.</p> <p>Methods</p> <p>Three hundred and forty-two life-long residents of a malaria-holoendemic region of western Kenya were enrolled in a cross-sectional study and stratified by age. We measured red cell C3b, CR1, CD55, and immune complex binding capacity by flow cytometry. 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 %C3b-positive red cells and the hemoglobin level.</p> <p>Results</p> <p>Individuals between the ages of 6 and 36 months had the lowest red cell CR1, highest %C3b-positive red cells, and highest parasite density. Malaria prevalence also reached its peak within this age group. Among children ≤ 24 months of age the %C3b-positive red cells was usually higher in individuals who were treated for malaria than in uninfected individuals with similarly low red cell CR1 and CD55. The variables that most strongly influenced the %C3b-positive red cells were age, malaria status, and red cell CD55 level. Although it did not reach statistical significance, red cell CR1 was more important than red cell CD55 among individuals treated for malaria. The variables that most strongly influenced the hemoglobin level were age, the %C3b-positive red cells, red cell CR1, and red cell CD55.</p> <p>Conclusion</p> <p>Increasing malaria prevalence among children >6 to ≤ 36 months of age in western Kenya, together with low red cell CR1 and CD55 levels, results in increased C3b deposition on red cells and low hemoglobin. The strong contribution of age to C3b deposition suggests that there are still additional unidentified age-related factors that increase the susceptibility of red cells to C3b deposition and destruction.</p

Castor Bean Metabolomics: Current Knowledge and Perspectives Toward Understanding of Plant Plasticity Under Stress Condition

Metabolomics provides vital information for the understanding of biological processes and has been vastly applied in plant studies. Several metabolite-profiling studies have correlated physiological events, such as germination or seedling establishment, with metabolic and molecular changes under different environmental conditions. Castor bean displays high plasticity during initial vegetative growth, which is reflected in the metabolome of the seeds and seedlings. In general, several metabolite-profiling techniques are required to obtain a complete response in terms of metabolism plasticity of the studied biological system. Carbohydrates, amino acids, and organic acids have been measured in castor bean seeds and seedlings by nuclear magnetic resonance, gas chromatography coupled to a quadrupole time of flight mass spectrometry (GC-TOF-MS), as well as by high-performance liquid chromatography (HPLC). Fatty acids and some secondary metabolites have been quantified in castor bean seeds and seedlings by gas chromatography coupled to a triple-axis detector (GC-MS). In this chapter, we initially discuss how metabolomics studies suggested a possible role of gamma-aminobutyric acid (GABA) accumulation during early imbibitions and seedling establishment. Later, we consider a specific metabolic signature of castor bean: a shift in carbon–nitrogen metabolism as its main biochemical response to high temperatures. This metabolic shift is usually associated with adjusted growth, and it is likely involved in maintaining cellular homeostasis under heat stress. The castor bean metabolome has been vastly investigated, especially with regard to its ability to respond to external stimuli. These results might help us understand the molecular requirements for vigorous castor bean seed germination and seedling growth under different environmental conditions