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)

The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.
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PMID:Molecular analysis of the association of HLA-B53 and resistance to severe malaria. 136 Jan 49

In mice, immune responses to subunits of defined malaria antigens are regulated by genes mapping within the MHC and it has been suggested that such genetic restriction will be a major obstacle in the development of a human malaria vaccine. The relationship between class II human leukocyte antigen (HLA) genes and immune recognition of three candidate antigens for a vaccine against Plasmodium falciparum malaria has been investigated in a human population living in a malaria endemic area of West Africa. The study population was shown to be extremely heterogeneous for HLA class II alleles and marked differences in allelic frequency were detected between members of different ethnic groups. One class II DQA-DQB combination (serological specificity DQw2) was particularly common among members of the Fula ethnic group. This haplotype was significantly associated with higher than average levels of antibody to a peptide epitope, (EENV)6, of the malaria antigen Pf155/RESA. There was little evidence of association between HLA class II genotype and cellular proliferative or interferon gamma responses to the antigens tested. Overall, the number of significant associations between immune responses and specific HLA class II haplotypes was greater than would be expected by chance but less than would be expected if class II-dependent genetic restriction were a major factor governing human immune responses to malaria antigens. Thus, although some qualitative variation in the immune response to vaccine antigens may occur in ethnically different target populations, widespread HLA-associated nonresponsiveness to a multivalent subunit malaria vaccine is unlikely.
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PMID:MHC and malaria: the relationship between HLA class II alleles and immune responses to Plasmodium falciparum. 139 Apr 36

Tumor necrosis factor alpha (TNF alpha) is a central mediator of the immunological response and the location of the gene within the major histocompatibility complex (MHC) has prompted much speculation about the role of TNF alpha alleles in inflammatory and MHC-associated autoimmune diseases. A G to A transition polymorphism at position -308 of the TNF alpha promoter/enhancer region has been described. The uncommon -308A allele was shown to be strongly associated with human leukocyte antigen (HLA)-DR3, known to be related to a TNF alpha "high producer" phenotype. In support for a clinical relevance, the -308A allele is implicated in susceptibility for cerebral malaria. In this study, we determined the junctional consequences of the TNF -308 polymorphism. Therefore, we analyzed both allelic forms (TNF alpha(-308G) and TNF alpha(-3O8A)) of the TNF alpha enhancer/promoter region (-598/+108) in a transient transfection system, using chloramphenicol acetyltransferase (CAT) as reporter gene. The T cell line Jurkat and the B cell line Raji served as hosts in these experiments. The results showed no differences in the level of inducible reporter gene expression between the TNF(-3O8G)/CAT and the TNF(-308A)/CAT constructs. These data were confirmed by allele specific TNF alpha transcript quantification (ASTQ) analysis, which demonstrated that both TNF alleles contribute equally to the total amount of mRNA in peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/anti-CD3. In analogy, no difference between the level of transcription of the -308A and -308G alleles was observed in lipopolysaccharide (LPS)-stimulated peripheral blood monocytes. This study indicates that the TNF alpha -308 G to A transition is not responsible for differential TNF alpha production induced by standard in vitro stimuli.
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PMID:Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. 883 66

Host-parasite coevolution has been likened to a molecular arms race, with particular parasite genes evolving to evade specific host defenses. Study of the variants of an antigenic epitope of Plasmodium falciparum that induces a cytotoxic T cell response supports this view. In African children with malaria, the variants present are influenced by the presence of a human leukocyte antigen (HLA) type that restricts the immune response to this epitope. The distribution of parasite variants may be further influenced by the ability of cohabiting parasite strains to facilitate each other's survival by down-regulating cellular immune responses, using altered peptide ligand antagonism.
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PMID:Association of malaria parasite population structure, HLA, and immunological antagonism. 950 87

DNA vaccine involves the injection of plasmid DNA encoding an antigen under the control of an eukaryotic promoter, and results in cellular and humoral immune responses to the plasmid DNA-encoded antigen. The immune response induced by DNA vaccine usually has a T-helper-1(Th1) bias through a potent Th1-promoting adjuvant effect of immunostimulatory DNA sequences with CpG motifs present in plasmid DNA. It has been demonstrated that volunteers who were vaccinated with plasmid DNA encoding a malaria protein or a human immunodeficiency virus protein developed antigen-specific, human leukocyte antigen(HLA)-restricted, CD8+ cytotoxic T lymphocytes(CTLs) The demonstration in humans of the induction of CD8+ CTLs by DNA vaccines, including CTLs, provides a foundation for further clinical application of this potentially revolutionary vaccine technology.
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PMID:[DNA vaccine]. 1151 28

Many human T-cell responses specific for epitopes in Plasmodium falciparum have been described, but none has yet been shown to be predictive of protection against natural malaria infection. Here we report a peptide-specific T-cell assay that is strongly associated with protection of humans in The Gambia, West Africa, from both malaria infection and disease. The assay detects interferon-gamma-secreting CD4(+) T cells specific for a conserved sequence from the circumsporozoite protein, which binds to many human leukocyte antigen (HLA)-DR types. The correlation was observed using a cultured, rather than an ex vivo, ELISPOT assay that measures central memory-'type T cells rather than activated effector T cells. These findings provide direct evidence for a protective role for CD4(+) T cells in humans, and a precise target for the design of improved vaccines against P. falciparum.
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PMID:A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease. 1503 67

We evaluated the proportion of variants of circumsporozoite protein (cp) gene 26 and cp29 antigenic epitopes of Plasmodium falciparum infecting patients among 3 provinces in western Thailand, in addition to published variants from Gambia. The proportion of patients coinfected with cp26 and cp29 strains was significantly higher in patients reporting to malaria clinics in Tak than in Kanchanaburi and Ratchaburi and higher in Kanchanaburi than in Ratchaburi. In western Thailand, coinfection with cp26 and cp29 appears to increase with increasing latitude. There were also significant differences in proportion of these variants among Thai provinces and Gambia. An association of patient human leukocyte antigen (HLA) class II genotype was associated with P. falciparum strains. There were significant associations among the HLA-DQA alleles in patients, the province of origin, and cp variants of P. falciparum.
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PMID:Variation of circumsporozoite 26 and 29 genotypes of Plasmodium falciparum infecting patients and association with HLA-DQA allotypes in western Thailand. 1504 Jun 90

In recent years, associations of particular factors of the human leukocyte antigen (HLA) system with two major infectious diseases of tropical countries have been recognized: common West African HLA antigens are associated with protection from severe Plasmodium falciparum malaria, and HLA-D alleles are associated with generalized disease, localized disease and putative immunity in Onchocerca volvulus infection. Here, Christian Meyer and Peter Kremsner summarize current information on the involvement of HLA factors in P. falciparum malaria and O. volvulus infection, and briefly report on HLA-related immunological characteristics of various conditions in these infectious diseases.
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PMID:Malaria and onchocerciasis: On HLA and related matters. 1527 11

The high degree of polymorphism of human leukocyte antigen (HLA) genes has been suggested to result from natural selection against susceptibility to a variety of infectious pathogens, including malaria. HLA molecules are considered to play a crucial role in the defense of the host against malarial infection, and different HLA class I and class II alleles have been reported to be associated with reduced susceptibility to malaria or the severity of malaria in different populations. To test for associations between HLA alleles and the severity of malaria in a Thai population, polymorphisms of HLA-B and HLA-DRB1 genes were investigated in 472 adult patients in northwest Thailand with Plasmodium falciparum malaria. In this study, malaria patients were classified into three groups: mild malaria, non-cerebral severe malaria, and cerebral malaria. Our results revealed that the allele frequencies of HLA-B46, -B56, and -DRB1*1001 were statistically different between non-cerebral severe malaria and cerebral malaria (P = 0.005), between mild malaria and cerebral malaria (P = 0.032), and between mild malaria and non-cerebral malaria (P = 0.007). However, our results may be showing false positives due to multiple testing. Thus, further study with a larger sample size must be conducted to obtain conclusive evidence of the association of these HLA-B and DRB1 alleles with the severity of malaria in Thailand.
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PMID:Polymorphisms of the HLA-B and HLA-DRB1 genes in Thai malaria patients. 1572 86

The vitamin D receptor (VDR) and the human leukocyte antigen (HLA) class II complex affect innate and/or adaptive immunity against Mycobacterium tuberculosis. HLA-DRB1, HLA-DQB1, and VDR gene (VDR) polymorphisms were previously associated with tuberculosis (TB) and are here investigated as candidates for TB susceptibility in the Venda population of South Africa. Genomic DNA from 95 patients with pulmonary tuberculosis (PTB) and 117 ethnically matched, healthy controls were typed for HLA-DRB1, DRB3, DRB4, DRB5, DQB1, and VDR polymorphisms FokI, BsmI, ApaI, and TaqI using polymerase chain reaction-sequence specific primers (PCR-SSP). Allele and haplotype frequencies were calculated by the estimator maximum (EM) algorithm. DRB1*1302 phenotype was significantly associated with TB occurring at a significantly higher allele frequency in cases than controls and found in haplotype with DQB1*0602/3. DQB1*0301-0304 phenotype was significantly associated with TB and found in haplotype with DRB1*1101-1121, showing significant linkage disequilibrium (LD) in both cases and controls. Only DRB1*1101-1121-DQB1*05 was significantly associated with TB based on the sequential Bonferroni p value. VDR SNP phenotypes were not associated with TB, but the haplotype F-b-A-T significantly protected from TB. In conclusion, common African HLA-DRB1 and -DQB1 variants, previously associated with protection from malaria and hepatitis B/C virus persistence, predispose the Venda to TB, whereas the proposedly active VDR haplotype F-b-A-T showed significant protection.
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PMID:Association of HLA-DR, -DQ, and vitamin D receptor alleles and haplotypes with tuberculosis in the Venda of South Africa. 1691 62


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