|
14th Annual Conference of the British HIV Association23-25 April 2008, Belfast |
EFFECT OF PD1.3 SINGLE NUCLEOTIDE POLYMORPHISM ON CD4 AND CD3 T CELL COUNTS IN HAART-TREATED CHRONIC HIV-1+ PATIENTS
HIV Med 2008 Apr 23-25 (Suppl 1);14:7 (abstract no. O27)
G Rosignoli1, N Liptrott2, N Imami1, M Bower1, F Gotch1 and A Owen2
1 Dept. of Immunology, Chelsea and Westminster Hospital, London, UK, 2 Pharmacology Group HIV, The University of Liverpool, Liverpool, UK
BACKGROUND: PD-1 and PD-L1 are negative regulators of T-cell activity, their expression has been linked to T-cell anergy and exhaustion. PD-1.3 is a single nucleotide polymorphism (SNP) which has been linked to autoimmune diseases such as systemic lupus erythematosis. In this study we have investigated the correlation between the presence of the PD-1.3 SNP and various immunological parameters.
METHODS: PBMC from 76 HAART treated chronic HIV-1 patients were collected and genomic DNA was ecxtracted genotyping was carried out using a RT allelic discrimination assay. In parallel PD-1 and PD-L1 expression levels were measured in CD4+ and CD8+ T-cell by flow cytometry and peripheral blood lymphocyte counts were carried out.
RESULTS: Of the 76 patients 14 were heterozygous (Het) carriers of the PD-1.3 SNP and 62 were wild type (WT) for this allele. The median CD3 count in the WT group was 1110 (IQR 789-1492) and 1376 (IQR 9232516) in the Het, the median CD4 count was 312 (IQR 176-476) for the WT and 552 (IQR 229-806) in the Het group. A significantly higher CD3 (p=0.0410) and CD4 (p=0.0466) T-cell count was observed in the PD-1.3 Het group compared to the WT. Overall no statistically significant difference was found between the two groups for PD-1 and PD-L1 expression in both CD8 and CD4 between Heterozygus and Wild type.
CONCLUSIONS: The presence of the PD-1.3 allele is associated with higher CD3 and CD4 T cell counts in chronically infected HIV-1 patients suggesting that this polymorphism influences the PD-1/PD-L1 pathway and confers protection to CD4 and CD3 T cells.
2008-04-23
O27
Copyright © 2008 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD