Immunogenetics

, Volume 57, Issue 9, pp 628–635

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 Nasi
  • Marcello Pinti
  • Roberto Bugarini
  • Leonarda Troiano
  • Enrico Lugli
  • Cristian Bellodi
  • Cristina Mussini
  • Vanni Borghi
  • Tommaso Trenti
  • Fiorella Balli
  • Roberto Esposito
  • Andrea Cossarizza
Original Paper

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 X2 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 

Abbreviations

NRTI

nucleosidic reverse transcriptase inhibitors

NNRTI

non-nucleosidic reverse transcriptase inhibitors

PI

protease inhibitors

HIV

human immunodeficiency virus

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Milena Nasi
    • 1
  • Marcello Pinti
    • 1
  • Roberto Bugarini
    • 1
  • Leonarda Troiano
    • 1
  • Enrico Lugli
    • 1
  • Cristian Bellodi
    • 1
    • 2
  • Cristina Mussini
    • 3
  • Vanni Borghi
    • 3
  • Tommaso Trenti
    • 4
  • Fiorella Balli
    • 5
  • Roberto Esposito
    • 3
  • Andrea Cossarizza
    • 1
    • 6
  1. 1.Department of Biomedical Sciences, Chair of ImmunologyUniversity of Modena and Reggio EmiliaModenaItaly
  2. 2.MRC Toxicology Unit, Section of Genetic InstabilityUniversity of LeicesterLeicesterUK
  3. 3.Department of Medical and Surgical Specialties, Clinic of Infectious and Tropical DiseasesUniversity of Modena and Reggio Emilia and Azienda PoliclinicoModenaItaly
  4. 4.Clinical Pathology ServicePavullo HospitalAUSL ModenaItaly
  5. 5.Department of PediatricsUniversity of Modena and Reggio EmiliaModenaItaly
  6. 6.Department of Biomedical Sciences, Section of General PathologyModenaItaly

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