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

• Published in: The Journal of infectious diseases Vol. 221; no. 7; pp. 1156 - 1166
• Main Authors: Kovacs, Andrea A Z, Kono, Naoko, Wang, Chia-Hao, Wang, Daidong, Frederick, Toni, Operskalski, Eva, Tien, Phyllis C, French, Audrey L, Minkoff, Howard, Kassaye, Seble, T. Golub, Elizabeth, Aouizerat, Bradley E, Kuniholm, Mark H, Millstein, Joshua
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 16.03.2020
• Subjects: Adolescent; Adult; Aged; Alleles; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; CD38 antigen; CD4 antigen; CD8 antigen; Cell activation; Cohort Studies; Coinfection - complications; Coinfection - epidemiology; Coinfection - genetics; Coinfection - immunology; DQA1 protein; Drb1 protein; Female; Genotype; Genotypes; Hepatitis; Hepatitis C; Hepatitis C - complications; Hepatitis C - epidemiology; Hepatitis C - genetics; Hepatitis C - immunology; Highly active antiretroviral therapy; Histocompatibility antigen HLA; HIV; HIV Infections - complications; HIV Infections - epidemiology; HIV Infections - genetics; HIV Infections - immunology; HLA Antigens - genetics; Human immunodeficiency virus; Humans; Lymphocyte Activation - genetics; Lymphocytes; Lymphocytes T; Major and Brief Reports; Middle Aged; Pathogenesis; Regression analysis; Womens health; Young Adult; HCV; HIV; HLA; immune activation; T-cell activation
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz589

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. We found that specific HLA alleles predict CD8 and CD4 T-cell activation, independent of HLA associations with viral load. These findings suggest that host genetic variation could affect risk for end-organ diseases through an immune activation mechanism.