HLA and malaria in four colombian ethnic groups

Restrepo, Mauricio; Rojas, William; Montoya, F.; Montoya, Asirid E.; Dawson, Deborah V.

doi:10.1590/s0036-46651988000500001

Cited by 5 publications

(2 citation statements)

References 4 publications

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“…Subsequently, several additional studies [42][43][44][45][46][47][48][49][50][51][52] summarized in Table 1 and reviewed by Ghosh [53] have explored an association between specific HLA antigens and malaria. The findings of these studies must be interpreted with caution because of the following problems: First, in all association studies between HLA factors and diseases, many statistical comparisons are made.…”

Section: Section 1: Plasmodium Falciparum Malaria and Abomentioning

confidence: 99%

Plasmodium falciparummalaria and the immunogenetics of ABO, HLA, and CD36 (platelet glycoprotein IV)

2010

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Plasmodium falciparum malaria has long been a killer of the young, and has selected for polymorphisms affecting not only erythrocytes, but the immunogenetics of three histocompatibility systems: ABO, human leukocyte antigen (HLA), and CD36. The ABO system is important because the original allele, encoding glycosylation with the A sugar, acts as an adhesion ligand with infected red blood cells (iRBC), thereby promoting vasoocclusion. The prevalence of blood group O, which reduces this cytoadhesion, has increased in endemic areas. Other adaptations which could mitigate A-mediated rosetting include weaker A expression and increased soluble A secretion. The role of the HLA system in malaria has been harder to verify. Although HLA-B53 and DRB1*04 may be associated with clinical outcome, HLA studies are challenged by numerous comparisons in this most polymorphic of systems, and confounded by increasingly heterogeneous populations. Certain HLA markers may also reflect linkage artefact with other malaria-relevant polymorphisms. HLA may be less important because the parasite predominantly invades a compartment which does not express HLA. Adhesion of iRBCs is also mediated by CD36, expressed on platelets, monocytes, and microvascular endothelium. CD36 on monocytes is involved in clearing iRBC, while CD36 on platelets and the endothelium may play a role in tissue sequestration. The genetics of CD36 expression are complex, and recent research is fraught with inconsistent results. The solution may lie in examining genotype-phenotype correlations, zygosity effects on differential tissue expression, or other mechanisms altering CD36 tissue expression. Carefully designed prospective studies should bridge the gap between in-vitro observations and clinical outcomes.

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Section: Section 1: Plasmodium Falciparum Malaria and Abomentioning

confidence: 99%

Plasmodium falciparummalaria and the immunogenetics of ABO, HLA, and CD36 (platelet glycoprotein IV)

2010

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“…The role of immune response-associated genes in determining human susceptibility to mild and/or severe malaria has been investigated in a number of epidemiological studies (Piazza et al 1973;Restrepo et al 1988;Hill et al 1991;Bennett et al 1993). There is evidence from one such study that specific class I and class II HLA alleles are associated with resistance to both cerebral malaria and severe malarial anaemia, and that malaria may have acted as a selective force on the HLA region (Hill et al 1991).…”

Section: Host Immune Response Genes and Susceptibility To Mild Or Sevmentioning

confidence: 99%

The role of MHC- and non-MHC-associated genes in determining the human immune response to malaria antigens

1996

Parasitology

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SUMMARYIndividual susceptibility to malaria infection, disease and death is influenced by host genotype, parasite virulence and a number of environmental factors including malaria-specific immunity. Immune responses are themselves determined by a combination of host genes and environmental effects. The extent to which host genotype limits the spectrum of possible immune responses may influence the outcome of infection and has consequences for vaccine design. Associations have been observed between human major histocompatibility complex (MHC) genotype and susceptibility to severe malaria, but no similar associations have been observed for mild malarial disease or for specific antibody responses to defined malaria antigens. Epidemiological studies have shown that, in practice, neither T helper cell nor antibody responses to malaria parasites are limited by host MHC genotype, but have revealed that genes lying outside the MHC may influence T cell proliferative responses. These genes have yet to be identified, but possible candidates include T cell receptor (TcR) genes, and genes involved in TcR gene rearrangements. More importantly, perhaps, longitudinal epidemiological studies have shown that the anti-malarial antibody repertoire is selective and becomes fixed in malaria-immune individuals, but is independent of host genotype. These findings suggest that the antibody repertoire may be determined, at least in part, by stochastic events. The first of these is the generation of the T and B cell repertoire, which results from random gene recombinations and somatic mutation and is thus partially independent of germline genes. Secondly, of the profusion of immunogenic peptides which are processed and presented by antigen presenting cells, a few will, by chance, interact with T and B cell surface antigen receptors of particularly high affinity. These T and B cell clones will be selected, will expand and may come to dominate the immune response, preventing the recognition of variant epitopes presented by subsequent infections - a process known as original antigenic sin or clonal imprinting. The immune response of an individual thus reflects the balance between genetic and stochastic effects. This may have important consequences for subunit vaccine development.

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