HLA and in vitro susceptibility to HIV infection

Jabri, Ali A. Al

doi:10.1016/s0161-5890(02)00023-8

Cited by 27 publications

(10 citation statements)

References 66 publications

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“…Strong immune responsiveness could also lead to more severe cell damage via molecular mimicry. The possible role of HLA in enterovirus-induced beta-cell damage is supported by the fact that HLA is known to modulate the clinical course of infectious diseases (malaria [17], HIV [18], HCV [19], HBV [20], HPV [21]). For example, HLA-DR3 is associated with severe illness and HLA-B27 with a benign illness during Hantavirus infection [22].…”

Section: Discussionmentioning

confidence: 99%

The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens

et al. 2003

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Aims/hypothesis. Enterovirus infections are among the environmental risk factors potentially contributing to the pathogenesis of Type 1 diabetes. The aim of this study was to evaluate virus-host interaction by analysing the enterovirus antibody levels in subjects carrying different HLA-DR alleles associated with either increased or decreased risk of Type 1 diabetes. Methods. Antibodies against coxsackievirus B4 were measured to study immune responses induced by natural enterovirus infections and against poliovirus 1 to study immune responses induced by immunisation by enterovirus antigens (vaccine). Antibodies against the mumps virus were measured as a control. Study subjects included siblings of children with Type 1 diabetes taking part in the Childhood Diabetes in Finland (DiMe) Study and carrying either HLA-DR risk (DR3 and/or DR4) or protective (DR2) alleles. Results. Children with either the HLA-DR3 or HLA-DR4 allele and those with both these risk alleles had higher Coxsackie B4 antibody levels than children carrying the HLA-DR2 allele (p=0.01, p=0.01 and p=0.008, respectively). High responders (IgG levels higher than 75 percent) were also more frequent among genetically susceptible children compared to children with the protective DR2 allele (27% vs 12%) (p<0.009). The same trend was seen for poliovirus antibodies, while mumps antibody levels had a different pattern (high responders more common among DR2-positive subjects). Conclusions/interpretation. Diabetes-associated HLA-DR risk alleles were associated with a strong immune responsiveness and protective alleles with a weak responsiveness against enterovirus antigens. This phenomenon should be taken into consideration in serological case-control studies and it might play a role in virus-induced beta-cell damage. [Diabetologia (2003[Diabetologia ( ) 46:1100[Diabetologia ( -1105

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Section: Discussionmentioning

confidence: 99%

The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens

et al. 2003

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“…10 In addition to their helper role, virus specific CD4 cells may directly curtail HIV spread by the secretion of antiviral factors. 11 In view of the known effects of HLA gene products on the immune response, there have been several attempts to correlate HLA gene polymorphisms with progression to disease following HIV infection [12][13][14] in particular using cohorts representing the extremes of rapid progression and non-progression. 15,16 In relation to class I HLA alleles, HLA-B14, -B27, -B57, and -B44 have been found to be associated with slower progression [17][18][19][20][21][22] while the HLA-A29, -B22 and B-35 alleles were associated with rapid disease progression.…”

Section: Introductionmentioning

confidence: 99%

Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T‐cell decline in human immunodeficiency virus‐1 infection

Vyakarnam¹,

Sidebottom

Murad³

et al. 2004

Immunology

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SUMMARYPolymorphism amongst the human leucocyte antigen (HLA) class II genes could influence antigen presentation and the ability to control human immunodeficiency virus (HIV)-1 by modulating the virus specific CD4 immune response. To examine the effect of such polymorphisms on disease progression, we studied a cohort of 46 HIV-1 infected long-term non-progressors (LTNPs), 87 intermediate progressors (IPs) and 26 rapid progressors. Kaplan-Meier survival analysis of all patients in the cohort on time to a CD4 count less than 350 cells/ll, showed a trend for a slower rate of CD4 decline in patients with, compared to those without, the DRB1*15-DQB1*06 haplotype (hazard ratio (HR) 0AE69, 95% CI 0AE46-1AE01, P = 0AE06). A similar effect was not observed with the DRB1*13-DQB1*06 haplotype (HR 1AE18, 95% CI 0AE75-1AE88, P = 0AE46), but was observed when DQB1*06 alleles were considered irrespective of their DR association (HR 0AE74, 95% CI 0AE52-1AE05, P = 0AE06). Major HLA-DQ6 alleles encode aspartate (Asp) at position 57 on the DQb chain, a phenotype associated with protection from other immune disorders. We therefore examined the frequency of all DQb57 Asp + alleles, but could not detect a significant effect on the rate of CD4 decline. To examine whether the genotype associated with slower CD4 decline was over-represented in patients with a slow rate of disease progression, we conducted a categorical analysis of a subset of patients with an extended follow-up of 14+years. We found a higher proportion of LTNPs at 14+ years possessed the DRB1*15-DQB1*06 haplotype compared to IPs at 14+ years (38AE46 versus 18AE18%), though this difference did not reach statistical significance. When DQB1*06 alleles irrespective of their DR association were considered, the protective effect was greater (76AE9% LTNPs versus 18AE18% IPs, P = 0AE04). Our results highlight the potential protective effect of HLA DQB1*06 alleles on the course of HIV disease.

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“…ue to the major role of the HLA locus in controlling the immune response, associations between HLA genes and progression to AIDS have been extensively studied (1,2). Various cohort studies have identified associations between HLA genes (class I and class II) and progression to AIDS.…”

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confidence: 99%

Associations of MHC Ancestral Haplotypes with Resistance/Susceptibility to AIDS Disease Development

Flores-Villanueva

Hendel

Caillat‐Zucman

et al. 2003

The Journal of Immunology

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We tested the association of MHC ancestral haplotypes with rapid or slow progression to AIDS by comparing their frequencies in the French genetics of resistance/susceptibility to immunodeficiency virus cohort with that reported in a control French population. Seven ancestral haplotypes were identified in the genetics of resistance/susceptibility to immunodeficiency virus cohort with a frequency >1%. The 8.1 (odds ratio (OR) = 3, p = 0.006), 35.1 (OR = 5.7, p = 0.001), and 44.2 (OR = 3.4, p = 0.007) ancestral haplotypes were associated with rapid progression, whereas the 35.2 (OR = 3.6, p = 0.001), 44.1 (OR = 5.4, p < 10−4), and 57.1 (OR = 5.8, p < 10−4) ancestral haplotypes were associated with slow progression to AIDS. Although the frequency of each ancestral haplotype is low in the population, the OR were quite higher than those previously obtained for single HLA allele associations, with some p values as low as 10−4. The analysis of the recombinant fragments of these haplotypes allowed the identification of the MHC regions in the 35.1, 35.2, and 44.2 haplotypes associated with rapid progression to AIDS and the MHC regions of the 44.1 and 57.1 haplotypes associated with slow progression to AIDS. Previous studies have identified single HLA alleles associated with disease progression. Our results on recombinant fragments confirm the direct role of HLA-B35 in rapid progression. Associations with HLA-A29 and -B57 might be due to linkage disequilibrium with other causative genes within the MHC region.

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HLA and in vitro susceptibility to HIV infection

Cited by 27 publications

References 66 publications

The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens

The HLA-DR phenotype modulates the humoral immune response to enterovirus antigens

Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T‐cell decline in human immunodeficiency virus‐1 infection

Associations of MHC Ancestral Haplotypes with Resistance/Susceptibility to AIDS Disease Development

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