Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T-cell decline in human immunodeficiency virus-1 infection
Article first published online: 6 APR 2004
Volume 112, Issue 1, pages 136–142, May 2004
How to Cite
Vyakarnam, A., Sidebottom, D., Murad, S., Underhill, J. A., Easterbrook, P. J., Dalgleish, A. G. and Peakman, M. (2004), Possession of human leucocyte antigen DQ6 alleles and the rate of CD4 T-cell decline in human immunodeficiency virus-1 infection. Immunology, 112: 136–142. doi: 10.1111/j.1365-2567.2004.01848.x
- Issue published online: 6 APR 2004
- Article first published online: 6 APR 2004
- Received 16 May 2003; revised 5 February 2004; accepted 12 February 2004.
- disease progression;
- HLA Class II;
- T cells: CD4+
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/µl, 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 DQβ chain, a phenotype associated with protection from other immune disorders. We therefore examined the frequency of all DQβ57 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.