Association of HLA Genotype With T-Cell Activation in Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus-Coinfected Women.
HCV
HIV
HLA
T-cell activation
immune activation
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
16 03 2020
16 03 2020
Historique:
received:
28
08
2019
accepted:
06
11
2019
pubmed:
6
12
2019
medline:
5
1
2021
entrez:
6
12
2019
Statut:
ppublish
Résumé
Global immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus . 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31802115
pii: 5618844
doi: 10.1093/infdis/jiz589
pmc: PMC7325713
doi:
Substances chimiques
HLA Antigens
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1156-1166Subventions
Organisme : NIAID NIH HHS
ID : R56 AI052065
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL146242
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000004
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI034989
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI052065
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000454
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA044111
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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