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• Associations of multi-locus polymorphisms in an immune network with susceptibility to uncomplicated Plasmodium falciparum malaria in Daraweesh village, Eastern Sudan

  2011. Hayder A. Giha (et al.). Infection, Genetics and Evolution 11 (7), 1674-1681

  Artikel

  Susceptibility to uncomplicated malaria (UM), as to other forms of the disease, is genetically determined. Over 9-years of clinical and parasitological follow up of inhabitants of Daraweesh, in Eastern Sudan, the relative susceptibility to UM was estimated in terms of number of episodes experienced by each individual. Previously, we reported that the levels of IgG2 and IgG3 to Pf332-C231 malaria antigen are negatively correlated with number of malaria episodes. In addition, four molecular markers for malaria susceptibility (CRP -286, GM/KM haplotypes, FcγRIIa131 and HbAS) were tested. In this study, the above data were combined and reanalysed. The CRP -286A allele and GM 1,17 5,13,14,6 phenotype were previously found to be associated with increased susceptibility to malaria; however, individuals have both polymorphism together were not more susceptible to UM than the non-carriers of the same double polymorphism. The FcγRIIa-RR131 and HbAA genotypes taken individually or as double polymorphism were not associated with malaria susceptibility; however, their combination with any or both of the former polymorphisms was mostly associated with increased susceptibility to malaria. None of the four markers were associated with the levels of IgG2 and IgG3 against Pf332-C231. In conclusion, while our data support the polygenic nature of susceptibility to UM and highlighted the role of immune markers polymorphisms, the combinations of these markers were not predictable, i.e. the combination of the susceptibility markers will not necessarily render the carriers more susceptible to UM.

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• Cytokine gene haplotypes with a potential effect on susceptibility to malaria in sympatric ethnic groups in Mali

  2011. Elisabeth Israelsson (et al.). Infection, Genetics and Evolution 11 (7), 1608-1615

  Artikel

  Cytokines are important players in the immune responses, and an unbalance in pro- and anti-inflammatory cytokine responses may affect parasitemia and pathology in a Plasmodium falciparum infection. Polymorphisms in cytokine genes may affect not only the levels of the protein, but many down-stream functions, such as production of C-reactive protein and immunoglobulin isotype switching. Susceptibility to malaria has been shown to differ between individuals with different genetic backgrounds, as indicated by studies in Fulani and non-Fulani ethnic groups. The aim of this study was to investigate possible interethnic differences in totally twelve single nucleotide polymorphisms (SNPs) in the genes encoding the cytokines IL-1β, IL-6, IL-10 and TNF. These SNPs are present in the promoter region of the genes, and have previously been associated with cytokine expression and with disease outcome in malaria. The results from the present study suggest that the Fulani ethnic group has a more pro-inflammatory response, due to high frequencies of high-producing alleles of IL1β and low-producing alleles of IL10. IL-6 could potentially also contribute to the relatively lower susceptibility to malaria in the Fulani ethnic group, whereas the TNF polymorphisms analysed in this study rather seem to associate with the severity of the infection and not the susceptibility for the infection itself. We therefore suggest that the polymorphisms analysed in this study all show a potential to influence the relatively lower susceptibility to malaria seen in the Fulani ethnic group as compared to the other sympatric ethnic groups.

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• Pattern of Pre-existing IgG Subclass Responses to a Panel of Asexual Stage Malaria Antigens Reported During the Lengthy Dry Season in Daraweesh, Sudan

  2011. A. Nasr (et al.). Scandinavian Journal of Immunology 74 (4), 390-396

  Artikel

  The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231. The results showed that the antibody responses were predominantly age dependent, antigen specific, and their lifespan was at least 5-6 month long. Generally, the IgG3 was most abundant IgG subclass, and the most recognized antigen was Pf332-C231. Furthermore, the correlation between the levels of IgG subclasses was strongest between IgG1 and IgG3, which were more predictive to the total IgG levels. Finally, the response pattern of each of the IgG subclasses to the different test antigens that were spanning the dry season and the correlation between these responses were described in details for the first time.

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• Antibodies to the Plasmodiumfalciparum antigen Pf332 cooperated with human monocytes inhibit parasitegrowth by inducing intraerythrocytic abnormal parasite forms in vitro

  Lili Xu (et al.).

  IntraerythrocyticPlasmodium parasite proliferation istightly related to disease seriousness. Intraerythrocytic parasite developmentis fundamental to the proliferation of the malaria parasite which is affectedby many factors. Antibodies inhibiting intraerythrocytic parasite growth ordevelopment have been long indicated in protective immune mechanisms,particularly in cooperation with human monocytes. Here, we show that the developmentP. falciparum intraerythrocyticparasite was significantly disturbed by antibodies reactive with theintraerythrocytic parasitic antigen Pf332 by inducing parasites with anabnormal morphology. A synergistic effect in the induction of the abnormal formswas seen when antibodies cooperated with human monocytes. The long period of 48hours intraerythrocytic development provides a greater opportunity for antibodiesto react with the intraerythrocytic antigens than with merozoite stage antigens,which are exposed only for a short period of time.

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