TY - JOUR
T1 - Association of HLA genotype with T-cell activation in human immunodeficiency virus (HIV) and HIV/ hepatitis c virus-coinfected women
AU - Kovacs, Andrea A.Z.
AU - Kono, Naoko
AU - Wang, Chia Hao
AU - Wang, Daidong
AU - Frederick, Toni
AU - Operskalski, Eva
AU - Tien, Phyllis C.
AU - French, Audrey L.
AU - Minkoff, Howard
AU - Kassaye, Seble
AU - Golub, Elizabeth T.
AU - Aouizerat, Bradley E.
AU - Kuniholm, Mark H.
AU - Millstein, Joshua
N1 - Funding Information:
Financial support. This work was supported by the National Institute of Allergy and Infectious Diseases: R56AI052065, R01AI052065, and the National Institute on Drug Abuse R01DA044111 (Andrea Kovacs, PI). This work was supported by the National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Dental and Craniofacial Research, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Deafness and other Communication Disorders, and the NIH’s Office of Research on Women’s Health, and the NIH (grants UL1-TR000004 [to University of California, San Francisco, Clinical & Translational Science Institute], UL1-TR000454 [to Atlanta Clinical & Translational Science Alliance], and P30-AI-050410 [to University of North Carolina Center for AIDS Research]).
Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2020/3/16
Y1 - 2020/3/16
N2 - 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.
AB - 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.
KW - HCV
KW - HIV
KW - HLA
KW - Immune activation
KW - T-cell activation
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U2 - 10.1093/infdis/jiz589
DO - 10.1093/infdis/jiz589
M3 - Article
C2 - 31802115
AN - SCOPUS:85082146109
VL - 221
SP - 1156
EP - 1166
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 7
ER -