title: 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.
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.
authors.affiliation: Department of Biomedical Sciences, Chair of Immunology, University of Modena and Reggio Emilia, via Campi 287, Modena, 41100, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Roberto
authors.initials: R
authors.lastname: Bugarini
authors.forename: Leonarda
authors.initials: L
authors.lastname: Troiano
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Cristian
authors.initials: C
authors.lastname: Bellodi
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Vanni
authors.initials: V
authors.lastname: Borghi
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
authors.forename: Fiorella
authors.initials: F
authors.lastname: Balli
authors.forename: Roberto
authors.initials: R
authors.lastname: Esposito
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D048069:Tumor Necrosis Factors / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D017320:HIV Protease Inhibitors; D008562:Membrane Glycoproteins; D018894:Reverse Transcriptase Inhibitors; D048069:Tumor Necrosis Factors; D019014:fas Receptor