Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Placenta-sequestering Plasmodium falciparum parasites causing pregnancy-associated malaria express pregnancy-specific variant surface antigens (VSA(PAM)). We report here that VSA(PAM)-expressing patient isolates adhere strongly to the choriocarcinoma cell line BeWo and that the BeWo line can be used to efficiently select for VSA(PAM) expression in vitro.
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PMID:Plasmodium falciparum parasites expressing pregnancy-specific variant surface antigens adhere strongly to the choriocarcinoma cell line BeWo. 1662 46

Available evidence suggests that, in African populations, systemic blood-dwelling parasitoses of mothers are associated with enhanced susceptibility to infection of their offspring. Thus, children born to mothers with filariasis or schistosomiasis are infected earlier, and offspring of mothers with placental Plasmodium falciparum at delivery, commonly referred to as pregnancy-associated malaria or PAM, are themselves at higher risk of developing parasitaemia during infancy. Since foetal/neonatal antigen-presenting cells (APC) are either immature or provide insufficient costimulatory signals to T cells, thus favouring tolerance induction, it is commonly assumed that soluble parasite components [protein antigens], transferred transplacentally and inducing foetal immune tolerance, are largely, if not exclusively, responsible for these outcomes. Plasmodial asexual blood stage antigen-specific T cells are detectable in as many as two-thirds of all cord blood samples in malaria-endemic countries of sub-Saharan Africa, indicating that in utero sensitization may be a common phenomenon during pregnancy in these populations. Parasite antigen-specific T cell responses of neonates born to helminth-infected mothers display a highly skewed Th2-type cytokine pattern, with a prominent role for the regulatory cytokine interleukin (IL)-10. Similarly, the cord blood immune response of those born to mothers identified with on-going PAM is characterised by inducible parasite antigen-specific IL-10-producing regulatory T cells that can inhibit both APC HLA expression and Th1-type T cell responses. In contrast, plasmodial antigen-specific Th1-type responses, characterised by IFN-gamma production, predominate in cord blood of those born to mothers successfully treated for Pf malaria during gestation, suggesting that the duration and/or the nature of antigen exposure in utero governs the outcome with respect to neonatal immune responses. Aspects of APC function in the context of these differentially modulated responses, whether and how the latter translate into altered susceptibility to Pf infection during infancy, as well as the possible implications for vaccination in early life, are aspects that are discussed in this review.
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PMID:Placental Plasmodium falciparum infection: causes and consequences of in utero sensitization to parasite antigens. 1708 34

Human immunodeficiency virus type 1 (HIV-1) coinfection decreases antibodies to variant surface antigens implicated in pregnancy-associated malaria (VSA-PAM) caused by Plasmodium falciparum. The effect of HIV-1 on antibody functions that may protect mothers from pregnancy-associated malaria is unknown. Sera from multigravid pregnant women with malaria and HIV-1 coinfection (n=58) or malaria alone (n=29) and from HIV-1-infected (n=102) or -uninfected (n=54) multigravidae without malaria were analyzed for anti-VSA-PAM antibodies by flow cytometry, the ability to inhibit adhesion to chondroitin sulfate A, or to opsonize CS2-infected erythrocytes for phagocytosis by THP-1 cells. In women with malaria, anti-VSA-PAM levels correlated better with opsonic activity (r=0.60) than with adhesion-blocking activity (r=0.33). In univariate analysis, HIV-1 coinfection was associated with lower opsonic activity but not adhesion-blocking activity or anti-VSA-PAM levels. Malaria-infected women with anemia (hemoglobin levels of <11.0 g/dl) had lower opsonic activity than nonanemic women (P=0.007) independent of HIV-1 status. By multivariate analysis, in malaria-infected women, anemia (but not HIV status) was associated with opsonic activity. In women without malaria, opsonic activity was not associated with either anemia or HIV-1 status. In multigravid pregnant women with malaria, impaired serum opsonic activity may contribute to anemia and possibly to the decreased immunity to pregnancy-associated malaria associated with HIV-1.
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PMID:Relationship between human immunodeficiency virus type 1 coinfection, anemia, and levels and function of antibodies to variant surface antigens in pregnancy-associated malaria. 1912 67

Malaria during pregnancy is a major health problem for African women. The disease is caused by Plasmodium falciparum malaria parasites, which accumulate in the placenta by adhering to chondroitin sulfate A (CSA). The interaction between infected erythrocytes and the placental receptor is mediated by a parasite expressed protein named VAR2CSA. A vaccine protecting pregnant women against placental malaria should induce antibodies inhibiting the interaction between VAR2CSA and CSA. Much effort has been put into defining the part of the 350 kDa VAR2CSA protein that is responsible for binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with high affinity, however to date no sub-fragment of VAR2CSA has been shown to interact with CSA with similar affinity or specificity. In this study, we used a biosensor technology to examine the binding properties of a panel of truncated VAR2CSA proteins. The experiments indicate that the core of the CSA-binding site is situated in three domains, DBL2X-CIDR(PAM) and a flanking domain, located in the N-terminal part of VAR2CSA. Furthermore, recombinant VAR2CSA subfragments containing this region elicit antibodies with high parasite adhesion blocking activity in animal immunization experiments.
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PMID:The chondroitin sulfate A-binding site of the VAR2CSA protein involves multiple N-terminal domains. 2139 24