Journal article
Human leukocyte antigen associations with protection against tuberculosis infection and disease in human immunodeficiency virus-1 infected individuals, despite household exposure and immune suppression
Tuberculosis, Vol.126, Art. 102023
2021
Abstract
Background
To determine the association of human leukocyte antigen (HLA) alleles as correlates of risk for and protection against tuberculin skin test (TST) positivity and active TB disease amongst HIV-infected adults.
Methods
Genomic DNA was extracted from 754 HIV-infected adults whole-blood. HLA-A, -B, -C and -DRB1 loci were genotyped by next generation sequencing methods. HLA alleles were analysed by the presence/absence of TST immune conversion and active TB disease and further stratified by exposure to a household TB contact, CD4 T-cell count and, for active TB disease, TST-positivity.
Results
HLA-A*29:11 and - B*45:01/07 were associated with TST-positivity, while HLA-A*24:02, -A*29:02 and -B*15:16 with TST-negativity. In participants with a household TB contact, HLA-A*66:01, -A*68:02 and -B*49:01 were associated with TST-negativity. For TB disease, HLA-B*41:01, -C*06:02, -DRB1*04:01 and -DRB1*15:01 were associated with susceptibility, while HLA-B*07:02 and -DRB1*11:01 were protective, even for CD4 T-cell count <350 cells/mm3. For initial TST-positivity and subsequent TB disease, HLA-A*01:01 and -DRB1*11:01 conveyed protection including those with CD4 T-cell count <350 cells/mm3.
Conclusion
Several HLA alleles are noted as correlates of TB infection, risk and natural protection in HIV-infected individuals. HLA associations may enable risk stratification of those with HIV infection. Protective alleles may assist in future TB vaccine development.
Details
- Title
- Human leukocyte antigen associations with protection against tuberculosis infection and disease in human immunodeficiency virus-1 infected individuals, despite household exposure and immune suppression
- Authors/Creators
- F. Seedat (Author/Creator) - University of the WitwatersrandI. James (Author/Creator) - Murdoch UniversityS. Loubser (Author/Creator) - National Health Laboratory ServiceZ. Waja (Author/Creator) - Chris Hani Baragwanath HospitalS. Mallal (Author/Creator) - Vanderbilt UniversityC. Hoffmann (Author/Creator) - Johns Hopkins UniversityC.T. Tiemessen (Author/Creator) - National Health Laboratory ServiceR.E. Chaisson (Author/Creator) - Johns Hopkins UniversityN.A. Martinson (Author/Creator) - Chris Hani Baragwanath Hospital
- Publication Details
- Tuberculosis, Vol.126, Art. 102023
- Publisher
- Elsevier Ltd
- Identifiers
- 991005541286607891
- Copyright
- © 2020 Elsevier Ltd.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.194 Tuberculosis & Leprosy
- 1.194.273 TB Diagnostics & Treatment
- Web Of Science research areas
- Immunology
- Microbiology
- Respiratory System
- ESI research areas
- Immunology