{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:52:35Z","timestamp":1787755955001,"version":"build-2784847793"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T00:00:00Z","timestamp":1574380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["KL2TR001879"],"award-info":[{"award-number":["KL2TR001879"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["K23AI134182"],"award-info":[{"award-number":["K23AI134182"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI120821"],"award-info":[{"award-number":["R01AI120821"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI045008"],"award-info":[{"award-number":["P30AI045008"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inflammasomes mediate inflammation in adults living with both human immunodeficiency virus (HIV) and tuberculosis (TB), but the relevance of inflammasome gene polymorphisms in TB-associated pulmonary damage is unknown. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in inflammasome pathway genes modify systemic and pulmonary inflammation, contributing to respiratory impairment in adults living with HIV\/pulmonary TB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective cohort study set in South Africa following individuals living with HIV\/TB up to 48 weeks post-antiretroviral therapy (ART) initiation. Ten functional SNPs in 5 inflammasome pathway genes were related to circulating inflammatory biomarkers and lung function assessed by spirometry pre- and post-ART initiation. Analyses used 2-sided t tests, Wilcoxon rank sum tests, Spearman correlation coefficients, linear regression, and generalized estimating equation models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 102 patients with baseline samples, the minor allele (T) in NLRC4 rs385076 was independently associated with lower levels of interleukin (IL)-18 and IL-6 before and up to 12 weeks post-ART initiation (Benjamini-Hochberg corrected P values &amp;lt; .02). Patients with the CT\/TT genotypes also had improved lung function vs CC patients up to 48 weeks post-ART initiation (forced vital capacity, 206 mL higher; 95% confidence interval [CI], 67\u2013345 mL; P = .004 and forced expiratory volume in 1 second, 143 mL higher; 95% CI, 11\u2013274 mL; P = .034).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A common SNP in the NLRC4 inflammasome may modify TB-associated inflammation in clinically relevant ways. This SNP may identify high-risk groups for lung damage in TB. Inhibition of NLRC4 activity may be an important approach for TB host-directed therapy.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz898","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T11:47:15Z","timestamp":1569584835000},"page":"924-932","source":"Crossref","is-referenced-by-count":24,"title":["A Common NLRC4 Gene Variant Associates With Inflammation and Pulmonary Function in Human Immunodeficiency Virus and Tuberculosis"],"prefix":"10.1093","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-9832","authenticated-orcid":false,"given":"Shruthi","family":"Ravimohan","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pholo","family":"Maenetje","sequence":"additional","affiliation":[{"name":"The Aurum Institute, 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline T","family":"Tiemessen","sequence":"additional","affiliation":[{"name":"Centre for HIV-1 and STIs, National Institute for Communicable Diseases, and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mboyo-Di-Tamba","family":"Vangu","sequence":"additional","affiliation":[{"name":"Nuclear Medicine, CM Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S","family":"Wallis","sequence":"additional","affiliation":[{"name":"The Aurum Institute, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Churchyard","sequence":"additional","affiliation":[{"name":"The Aurum Institute, Johannesburg, South Africa"},{"name":"School of Public Health, University 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