The association of class II HLA alleles with tuberculosis-associated immune reconstitution inflammatory syndrome
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Genetic associations within the human leukocyte antigen (HLA) gene complex and linked genes in TB-IRIS outcomes remains population specific and not well understood. Here, we conducted a study including well characterised HIV-TB coinfected patients with (n = 86) and without (n = 124) TB-IRIS from the randomized, double-blind, prophylactic prednisone trial (PredART study) with HLA, ERAP and KIR genotyping data. We confirmed the association of TB-IRIS with lower CD4 counts pre-ART initiation. We identified nine classical class I and II HLA alleles protective against TB-IRIS, while four alleles were linked to increased risk. Associations ranged from strongly protective (HLA-DQB1*05:01, OR: 0.07, 95%CI: 0.02-0.28, Pc < 0.001) to strongly risk associated (notably DRB1*01:02, OR: 5.92, 95%CI: 1.36-26.7, Pc = 0.028), with conflicting signals at the HLA-DRB1 locus. Conditional regression analysis revealed that residue E71 at the polymorphic position 71 within the HLA-DRB1 peptide-binding groove was critical, and grouping of HLA-DRB1 alleles by the residue at position 71 corresponded with differential TB-IRIS association. In conclusion, this study identifies population-specific genetic factors influencing TB-IRIS susceptibility and highlights a potential mechanistic role for specific HLA-DRB1 residues in modulating immune responses during ART.
Editor(s)
Koup, Richard A
Date Issued
2025-09-19
Date Acceptance
2025-08-29
Citation
PLoS Pathogens, 2025, 21 (9)
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
21
Issue
9
Copyright Statement
© 2025 Choshi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40972103
PII: PPATHOGENS-D-25-01617
Subjects
DISEASE
HAPLOTYPES
HLA-DR1
Life Sciences & Biomedicine
MHC
Microbiology
Parasitology
Science & Technology
Virology
Publication Status
Published
Coverage Spatial
United States
Article Number
e1013497
Date Publish Online
2025-09-19