Association of HLA Genotype With T-Cell Activation in Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus-Coinfected Women

Andrea A.Z. Kovacs, Naoko Kono, Chia Hao Wang, Daidong Wang, Toni Frederick, Eva Operskalski, Phyllis C. Tien, Audrey L. French, Howard Minkoff, Seble Kassaye, Elizabeth T Golub, Bradley E. Aouizerat, Mark H. Kuniholm, Joshua Millstein

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus . METHODS: We evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10. RESULTS: Ten HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, -6.6% [P = .002]; CD4 T cells, -2.7% [P = .007]), C*18:01 (CD8 T cells, -6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, -2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03. CONCLUSION: These findings suggest that a person's HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.

Original languageEnglish (US)
Pages (from-to)1156-1166
Number of pages11
JournalThe Journal of infectious diseases
Volume221
Issue number7
DOIs
StatePublished - Mar 16 2020

Keywords

  • HCV
  • HIV
  • HLA
  • immune activation
  • T-cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Kovacs, A. A. Z., Kono, N., Wang, C. H., Wang, D., Frederick, T., Operskalski, E., Tien, P. C., French, A. L., Minkoff, H., Kassaye, S., T Golub, E., Aouizerat, B. E., Kuniholm, M. H., & Millstein, J. (2020). Association of HLA Genotype With T-Cell Activation in Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus-Coinfected Women. The Journal of infectious diseases, 221(7), 1156-1166. https://doi.org/10.1093/infdis/jiz589