TY - JOUR
T1 - Human leukocyte antigen associations with protection against tuberculosis infection and disease in human immunodeficiency virus-1 infected individuals, despite household tuberculosis exposure and immune suppression
AU - Seedat, Faheem
AU - James, Ian
AU - Loubser, Shayne
AU - Waja, Ziyaad
AU - Mallal, Simon A.
AU - Hoffmann, Christopher
AU - Tiemessen, Caroline T.
AU - Chaisson, Richard E.
AU - Martinson, Neil A.
N1 - Funding Information:
The study of HIV-associated lung infections in Soweto was funded by the National Institutes of Health , USA ( R01HL090312 and P30AI094189 : R. E. Chaisson). This work is based on the research supported by grants awards from the Strategic Health Innovation Partnerships (SHIP) Unit of the South African Medical Research Council , a grantee of the Bill & Melinda Gates Foundation , and the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa.
Publisher Copyright:
© 2020 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - 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 for 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.
AB - 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 for 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.
KW - Active TB disease
KW - Correlates of protection
KW - HLA alleles
KW - Latent TB infection
KW - TST immune conversion
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U2 - 10.1016/j.tube.2020.102023
DO - 10.1016/j.tube.2020.102023
M3 - Article
C2 - 33249336
AN - SCOPUS:85096854273
SN - 1472-9792
VL - 126
JO - Tuberculosis
JF - Tuberculosis
M1 - 102023
ER -