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

doi:10.1093/infdis/jiz589

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

Oral and Maxillofacial Surgery

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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 language	English (US)
Pages (from-to)	1156-1166
Number of pages	11
Journal	Journal of Infectious Diseases
Volume	221
Issue number	7
DOIs	https://doi.org/10.1093/infdis/jiz589
State	Published - Mar 16 2020

Keywords

HCV
HIV
HLA
Immune activation
T-cell activation
Humans
Middle Aged
Hepatitis C/complications
Coinfection/complications
Genotype
HLA Antigens/genetics
Antiretroviral Therapy, Highly Active
Young Adult
HIV Infections/complications
Lymphocyte Activation/genetics
Adolescent
Adult
Female
Aged
Cohort Studies

ASJC Scopus subject areas

Infectious Diseases
Immunology and Allergy

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10.1093/infdis/jiz589

Cite this

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., Golub, E. T., 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. Journal of Infectious Diseases, 221(7), 1156-1166. https://doi.org/10.1093/infdis/jiz589

Kovacs, AAZ, Kono, N, Wang, CH, Wang, D, Frederick, T, Operskalski, E, Tien, PC, French, AL, Minkoff, H, Kassaye, S, Golub, ET, Aouizerat, BE, Kuniholm, MH & Millstein, J 2020, 'Association of HLA genotype with T-cell activation in human immunodeficiency virus (HIV) and HIV/ hepatitis c virus-coinfected women', Journal of Infectious Diseases, vol. 221, no. 7, pp. 1156-1166. https://doi.org/10.1093/infdis/jiz589

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title = "Association of HLA genotype with T-cell activation in human immunodeficiency virus (HIV) and HIV/ hepatitis c virus-coinfected women",

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.",

keywords = "HCV, HIV, HLA, Immune activation, T-cell activation, Humans, Middle Aged, Hepatitis C/complications, Coinfection/complications, Genotype, HLA Antigens/genetics, Antiretroviral Therapy, Highly Active, Young Adult, HIV Infections/complications, Lymphocyte Activation/genetics, Adolescent, Adult, Female, Aged, Cohort Studies",

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

note = "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{\textquoteright}s Office of Research on Women{\textquoteright}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: {\textcopyright} The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.",

year = "2020",

month = mar,

day = "16",

doi = "10.1093/infdis/jiz589",

language = "English (US)",

volume = "221",

pages = "1156--1166",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "7",

}

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

KW - Humans

KW - Middle Aged

KW - Hepatitis C/complications

KW - Coinfection/complications

KW - Genotype

KW - HLA Antigens/genetics

KW - Antiretroviral Therapy, Highly Active

KW - Young Adult

KW - HIV Infections/complications

KW - Lymphocyte Activation/genetics

KW - Adolescent

KW - Adult

KW - Female

KW - Aged

KW - Cohort Studies

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U2 - 10.1093/infdis/jiz589

DO - 10.1093/infdis/jiz589

M3 - Article

C2 - 31802115

AN - SCOPUS:85082146109

SN - 0022-1899

VL - 221

SP - 1156

EP - 1166

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 7

ER -

Association of HLA genotype with T-cell activation in human immunodeficiency virus (HIV) and HIV/ hepatitis c virus-coinfected women

Abstract

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ASJC Scopus subject areas

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