Abstract
Aim of the StudyAssociation of two HLA class I variants with HIV-1 pretreatment viremia, CD4+ T cell count at the care-entry and CD4+ T cell nadir.Methods414 HIV-positive Caucasians (30% women) aged 19-73 years were genotyped for HLA-C -35 (rs9264942) and HLA-B*5701 variants. HIV-1 viral load, as well as CD4+ T cell count at care-entry and nadir, were compared across alleles, genotypes and haplotypes.ResultsHLA-C -35 C/C genotype was found in 17.6% patients, C/T genotype in 48.1%, and T/T genotype in 34.3% patients. HLA-B*5701 variant was present in 5.8% of studied population. HIV plasma viremia in the group with C allele was significantly lower (p=0.0002) compared to T/T group [mean:4.66 log (SD:1.03) vs. 5.07 (SD:0.85) log HIV-RNA copies/ml, respectively], while CD4+ T cell count at baseline was notably higher among C allele carriers compared to T/T homozygotes [median: 318 (IQR:127-537) cells/μl vs. median: 203 (IQR:55-410) cells/μl, respectively] (p=0.0007). Moreover, CD4+ T cell nadir among patients with C allele [median: 205 (IQR:83.5-390) cells/μl] was significantly higher compared to T/T group [median: 133 (IQR:46-328) cells/μl] (p=0.006). Among cases with HLA-B*5701 allele, significantly lower pretreatment viremia and higher baseline CD4+ T cell count were found (mean: 4.08 [SD: 1.2] vs. mean: 4.84 [SD:0.97] log HIV-RNA copies/ml, p=0.003 and 431 vs. 270 cells/μl, p=0.04, respectively) compared to HLA-B*5701 negative individuals. The lowest viremia (mean: 3.85 log [SD:1.3]) HIV-RNA copies/ml and the highest baseline and nadir CD4+ T cell [median: 476 (IQR:304-682) vs. median: 361 (IQR: 205-574) cells/μl, respectively) were found in individuals with HLA-B*5701(+)/HLA-C –35 C/C haplotype.ConclusionsHLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological (higher baseline and nadir CD4+ T cell count) and virologic (lower pretreatment HIV viral load) variables. This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/C haplotype.
Highlights
Human leukocyte antigens C (HLA-C) strongly influence immunological activity in chronic viral infections (HCV, HIV) as well as in autoimmune diseases e.g. Crohn’s disease, autoimmune liver diseases, Graves’ disease and psoriasis vulgaris [1,2,3,4,5].HLA-C antigens play an important role in HIV control through two mechanisms: acting as ligands for killer immunoglobulin-like receptors (KIRs) presented on natural killer (NK) cells and directly by antigen presentation to cytotoxic T cells [1,6,7].The degree of NK cell activation or inhibition depends, inter alia, on the level of HLA-C expression [8]
HLA-C -35 C and HLA-B*5701 allele exert a favorable effect on the immunological and virologic variables
This protective effect is additive for the compound HLA-B*5701(+)/HLA-C -35 C/ C haplotype
Summary
Human leukocyte antigens C (HLA-C) strongly influence immunological activity in chronic viral infections (HCV, HIV) as well as in autoimmune diseases e.g. Crohn’s disease, autoimmune liver diseases, Graves’ disease and psoriasis vulgaris [1,2,3,4,5].HLA-C antigens play an important role in HIV control through two mechanisms: acting as ligands for killer immunoglobulin-like receptors (KIRs) presented on natural killer (NK) cells and directly by antigen (e.g. viral) presentation to cytotoxic T cells [1,6,7].The degree of NK cell activation or inhibition depends, inter alia, on the level of HLA-C expression [8]. HLA-C single nucleotide polymorphism (SNP) rs9264942 in locus -35 was found to be associated with differences in HIV-1 viremia in antiretroviral naive individuals [4,7,9,10,11,12,13,14]. The mechanism of this phenomenon is most likely related to differences in the HLA-C mRNA and surface expression levels between the -35 C and T allele carriers [9]. HLA-C is much less efficient in presenting antigen to cytotoxic T lymphocytes than HLA-A and HLA-B [17]
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