Genetic polymorphisms of Fas (CD95) and Fas ligand (CD178) influence the rise in CD4+ T cell count after antiretroviral therapy in drug-naïve HIV-positive patients

Immunogenetics. 2005 Oct;57(9):628-35. doi: 10.1007/s00251-005-0031-z. Epub 2005 Oct 18.

Abstract

Fas and Fas ligand (FasL) are the main genes that control cell death in the immune system. Indeed, they are crucial for the regulation of T lymphocyte homeostasis because they can influence cell proliferation. A strong debate exists on the importance of Fas/FasL system during HIV infection, which is characterized by the loss of CD4+ T cells directly, or indirectly, caused by the virus. To investigate whether the genetic background of the host plays a role in the immunoreconstitution, we studied the influence of different Fas and FasL polymorphisms on CD4+ T lymphocyte count and plasma viral load following initiation of highly active antiretroviral therapy (HAART) in drug-naïve HIV+ patients. We studied 131 individuals, who were compared to 136 healthy donors. Statistical analysis was performed by using Chi2 test, Fischer's Exact Test, and analysis for repeated measurements. The group of HIV+ patients had an unexpected lower frequency of FasLnt169 polymorphism (delT allele) than healthy controls (p = 0.039). We then observed no significant differences in the immune reconstitution, in terms of CD4+ T cell increase, when the influence of single alleles of the gene Fas or FasL was considered. However, the combination of some polymorphisms of Fas or FasL significantly influenced CD4+ T cell production and viral load decrease, showing that these genes can play a role in the immunoreconstitution triggered by antiretroviral therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Antiretroviral Therapy, Highly Active*
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / pathology
  • Fas Ligand Protein
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / immunology
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Lymphocyte Count
  • Male
  • Membrane Glycoproteins / genetics*
  • Middle Aged
  • Polymorphism, Genetic*
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Tumor Necrosis Factors / genetics*
  • fas Receptor / genetics*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • HIV Protease Inhibitors
  • Membrane Glycoproteins
  • Reverse Transcriptase Inhibitors
  • Tumor Necrosis Factors
  • fas Receptor