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

Tuberculosis (Edinb). 2021 Jan:126:102023. doi: 10.1016/j.tube.2020.102023. Epub 2020 Nov 19.

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 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.

Keywords: Active TB disease; Correlates of protection; HLA alleles; Latent TB infection; TST immune conversion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • CD4 Lymphocyte Count
  • Comorbidity
  • DNA, Viral / analysis
  • Family Characteristics*
  • Female
  • Follow-Up Studies
  • HIV Infections / epidemiology
  • HIV Infections / immunology*
  • HIV Infections / virology*
  • HIV-1 / genetics*
  • HLA Antigens / genetics*
  • Humans
  • Incidence
  • Latent Tuberculosis / epidemiology
  • Latent Tuberculosis / immunology*
  • Latent Tuberculosis / microbiology
  • Male
  • Mycobacterium tuberculosis / immunology*
  • Prospective Studies
  • South Africa / epidemiology
  • Tuberculin Test

Substances

  • DNA, Viral
  • HLA Antigens