{"doi":"10.1371/journal.ppat.1013497","title":"The association of class II HLA alleles with tuberculosis-associated immune reconstitution inflammatory syndrome","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.","journal":"PLoS Pathogens","year":2025,"id":547014,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":878672,"name":"Sarah Pedretti","orcid":"0000-0003-4005-8453","position":1,"is_corresponding":false},{"id":878668,"name":"Tafadzwa Chimbetete","orcid":"0000-0001-6972-4718","position":2,"is_corresponding":false},{"id":693147,"name":"Rama Gangula","orcid":null,"position":3,"is_corresponding":false},{"id":371678,"name":"Muki Shey","orcid":"0000-0002-8776-4737","position":4,"is_corresponding":false},{"id":560703,"name":"Cari Stek","orcid":"0000-0001-8813-0819","position":5,"is_corresponding":false},{"id":418472,"name":"Rachel Lai","orcid":"0000-0003-3418-850X","position":6,"is_corresponding":false},{"id":266683,"name":"Robert J. Wilkinson","orcid":"0000-0002-2753-1800","position":7,"is_corresponding":false},{"id":292884,"name":"Graeme Meintjes","orcid":"0000-0003-1196-4414","position":8,"is_corresponding":false},{"id":106289,"name":"Elizabeth J. Phillips","orcid":"0000-0002-7623-3383","position":9,"is_corresponding":false},{"id":301934,"name":"Jonny Peter","orcid":"0000-0002-2658-0723","position":10,"is_corresponding":false},{"id":878670,"name":"Phuti Choshi","orcid":"0000-0001-8860-9635","position":0,"is_corresponding":true}],"reference_count":24,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40972103","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}