title: Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T-cell decline in human immunodeficiency virus-1 infection.
abstract: Polymorphism 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/ micro l, 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) 0.69, 95% CI 0.46-1.01, P = 0.06). A similar effect was not observed with the DRB1*13-DQB1*06 haplotype (HR 1.18, 95% CI 0.75-1.88, P = 0.46), but was observed when DQB1*06 alleles were considered irrespective of their DR association (HR 0.74, 95% CI 0.52-1.05, P = 0.06). Major HLA-DQ6 alleles encode aspartate (Asp) at position 57 on the DQbeta chain, a phenotype associated with protection from other immune disorders. We therefore examined the frequency of all DQbeta57 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 (38.46 versus 18.18%), though this difference did not reach statistical significance. When DQB1*06 alleles irrespective of their DR association were considered, the protective effect was greater (76.9% LTNPs versus 18.18% IPs, P = 0.04). Our results highlight the potential protective effect of HLA DQB1*06 alleles on the course of HIV disease.
authors.affiliation: Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, London, UK. anna.vyakarnam@kcl.ac.uk
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
authors.forename: David
authors.initials: D
authors.lastname: Sidebottom
authors.forename: Shahed
authors.initials: S
authors.lastname: Murad
authors.forename: James A
authors.initials: JA
authors.lastname: Underhill
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Easterbrook
authors.forename: Angus G
authors.initials: AG
authors.lastname: Dalgleish
authors.forename: Mark
authors.initials: M
authors.lastname: Peakman
mesh_terms: D000483:Alleles; D001224:Aspartic Acid / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C053186:HLA-DQ2 antigen; C063831:HLA-DQ6 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D001224:Aspartic Acid