Andrea A Z Kovacs1, Naoko Kono2, Chia-Hao Wang1,3, Daidong Wang1, Toni Frederick1, Eva Operskalski1, Phyllis C Tien4, Audrey L French5, Howard Minkoff6, Seble Kassaye7, Elizabeth T Golub8, Bradley E Aouizerat9,10, Mark H Kuniholm11, Joshua Millstein2. 1. Department of Pediatrics, Maternal, Child and Adolescent Center for Infectious Diseases and Virology, Keck School of Medicine, University of Southern California, Los Angeles, California. 2. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. 3. City of Hope National Medical Center, Duarte, California. 4. Department of Medicine, University of California, San Francisco and Department of Veterans Affairs, San Francisco, California. 5. Department of Medicine, Stroger Hospital of Cook County/CORE Center, Rush Medical School, Chicago, Illinois. 6. Departments of Obstetrics and Gynecology Maimonides Medical Center and SUNY Downstate, Brooklyn, New York. 7. Department of Medicine, Georgetown University School of Medicine, Washington, DC. 8. Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland. 9. Bluestone Center for Clinical Research, New York University, New York, New York. 10. Department of Oral and Maxillofacial Surgery, New York University, New York, New York. 11. Department of Epidemiology and Biostatistics, University at Albany, State University of New York, Rensselaer, New York.
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.
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.
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