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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

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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.

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Abbreviations

NRTI:

nucleosidic reverse transcriptase inhibitors

NNRTI:

non-nucleosidic reverse transcriptase inhibitors

PI:

protease inhibitors

HIV:

human immunodeficiency virus

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Acknowledgements

We acknowledge Professor Judith A. Aberg (Washington University, St. Louis, MO, USA) and Professor Domenico Lio (University of Palermo, Italy) for helpful comments and critical reading of the manuscript. Supported by Istituto Superiore di Sanità (Programma Nazionale di Ricerca sull'AIDS, grant 40F.30, to A.C.). All the experiments comply with current Italian laws.

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Correspondence to Andrea Cossarizza.

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Nasi, M., Pinti, M., Bugarini, R. et al. 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 57, 628–635 (2005). https://doi.org/10.1007/s00251-005-0031-z

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  • DOI: https://doi.org/10.1007/s00251-005-0031-z

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