Expression of specific HLA class II alleles is associated with an increased risk for active tuberculosis and a distinct gene expression profile
HLA : immune response genetics, Vol.101(2), pp.124-137
2023
: 36373948
Several HLA allelic variants have been associated with protection from or susceptibility to infectious and autoimmune diseases. Here, we examined whether specific HLA alleles would be associated with different Mycobacterium tuberculosis (Mtb) infection outcomes. The HLA alleles present at the ‐A, ‐B, ‐C, ‐DPA1, ‐DPB1, ‐DQA1, ‐DQB1, ‐DRB1, and ‐DRB3/4/5 loci were determined in a cohort of 636 individuals with known Mtb infection outcomes from South Africa and the United States. Among these individuals, 203 were QuantiFERON (QFT) negative, and 433 were QFT positive, indicating Mtb exposure. Of these, 99 QFT positive participants either had active tuberculosis (TB) upon enrollment or were diagnosed in the past. We found that DQA1*03:01, DPB1*04:02, and DRB4*01:01 were significantly more frequent in individuals with active TB (susceptibility alleles), as judged by Odds Ratios and associated p‐values, while DPB1*105:01 was associated with protection from active TB. Peripheral blood mononuclear cells (PMBCs) from a subset of individuals were stimulated with Mtb antigens, revealing individuals who express any of the three susceptibility alleles were associated with lower magnitude of responses. Furthermore, we defined a gene signature associated with individuals expressing the susceptibility alleles that was characterized by lower expression of APC‐related genes. In summary, we have identified specific HLA alleles associated with susceptibility to active TB and found that the expression of these alleles was associated with a decreased Mtb‐specific T cell response and a specific gene expression signature. These results will help understand individual risk factors in progressing to active TB.
- Expression of specific HLA class II alleles is associated with an increased risk for active tuberculosis and a distinct gene expression profile
- Leila Y. Chihab - La Jolla Institute for ImmunologyRebecca Kuan - La Jolla Institute for ImmunologyElizabeth J. Phillips - Murdoch UniversitySimon A. Mallal - Vanderbilt University School of MedicineVirginie Rozot - South African Tuberculosis Vaccine InitiativeMark M. Davis - Stanford University School of MedicineThomas J. Scriba - South African Tuberculosis Vaccine InitiativeAlessandro Sette - University of California San DiegoBjoern Peters - La Jolla Institute for ImmunologyCecilia S. Lindestam Arlehamn - La Jolla Institute for ImmunologySATVI Study Group
- HLA : immune response genetics, Vol.101(2), pp.124-137
- John Wiley & Sons Ltd.
- 14
- S10 OD016262 S10 RR027366 National Institutes of Health U19 AI118626
- 991005567368207891
- © 2022 The Authors.
- Institute for Immunology and Infectious Diseases
- English
- Journal article
157
40
research.portal.fulldisplay.incitesHighlights.intro
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- 1 Clinical & Life Sciences
- 1.6 Immunology
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- Immunology
- Pathology
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- Molecular Biology & Genetics