Original Paper

Immunogenetics

, Volume 57, Issue 9, pp 628-635

First online:

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

  • Milena NasiAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia
  • , Marcello PintiAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia
  • , Roberto BugariniAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia
  • , Leonarda TroianoAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia
  • , Enrico LugliAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia
  • , Cristian BellodiAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio EmiliaMRC Toxicology Unit, Section of Genetic Instability, University of Leicester
  • , Cristina MussiniAffiliated withDepartment of Medical and Surgical Specialties, Clinic of Infectious and Tropical Diseases, University of Modena and Reggio Emilia and Azienda Policlinico
  • , Vanni BorghiAffiliated withDepartment of Medical and Surgical Specialties, Clinic of Infectious and Tropical Diseases, University of Modena and Reggio Emilia and Azienda Policlinico
  • , Tommaso TrentiAffiliated withClinical Pathology Service, Pavullo Hospital
    • , Fiorella BalliAffiliated withDepartment of Pediatrics, University of Modena and Reggio Emilia
    • , Roberto EspositoAffiliated withDepartment of Medical and Surgical Specialties, Clinic of Infectious and Tropical Diseases, University of Modena and Reggio Emilia and Azienda Policlinico
    • , Andrea CossarizzaAffiliated withDepartment of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio EmiliaDepartment of Biomedical Sciences, Section of General Pathology Email author 

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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 X 2 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.

Keywords

AIDS HIV HAART Apoptosis CD95/Apo-1/Fas gene polymorphism CD178/CD95L/FasL gene polymorphism