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 journalArticlepeer-review

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
JournalJournal of Infectious Diseases
Volume221
Issue number7
DOIs
StatePublished - 2020

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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