ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020
A Common NLRC4 Gene Variant Associates With Inflammation and Pulmonary Function in Human Immunodeficiency Virus and Tuberculosis.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 27 citations in OpenAlex.
- NLR Inflammasomes in Viral Infections: From Molecular Mechanisms to Therapeutic Interventions.Viruses · 2026Review
- Clinical and transcriptomic risk factors for post-tuberculosis lung disease in a cohort of Kenyan adults.American journal of respiratory and critical care medicine · 2026Observational
- NLRC4 and NLRP3 in tissues as potential biomarkers for the diagnosis of non-small cell lung cancer in pulmonary tuberculosis.Frontiers in cellular and infection microbiology · 2026Article
- Plasma NLRC4 and NLRP3 as potential diagnostic biomarkers for non-small cell lung cancer in pulmonary tuberculosis.Discover oncology · 2025Article
- Targeting inflammasomes as a therapeutic potential for HIV/AIDS.Cellular and molecular life sciences : CMLS · 2025Review
- Inclusion of patient-centered, non-microbiological endpoints and biomarkers in tuberculosis drug trials.Frontiers in antibiotics · 2025Review
- Inflammasome-Related Genetic Polymorphisms as Severity Biomarkers of COVID-19.International journal of molecular sciences · 2024Article
- The influence of pyroptosis-related genes on the development of chronic obstructive pulmonary disease.BMC pulmonary medicine · 2023Article
- Inflammasomes as mediators of inflammation in HIV-1 infection.Translational research : the journal of laboratory and clinical medicine · 2023Review
- HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model.Frontiers in immunology · 2023Article
- Pyroptosis and Inflammasome-Related Genes-Pharmacogenomics and personalized medicine · 2023Article
- NLRC4-mediated activation of CD1c+ DC contributes to perpetuation of synovitis in rheumatoid arthritis.JCI insight · 2022Article
- Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.Frontiers in cellular and infection microbiology · 2022Article
- Gain-of-Function Polymorphisms in Human Inflammasomes: Implications for Cystic Fibrosis.American journal of respiratory cell and molecular biology · 2021Article
- Classical complement and inflammasome activation converge in CD14highCD16- monocytes in HIV associated TB-immune reconstitution inflammatory syndrome.PLoS pathogens · 2021Article
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- Polymorphisms of theDiabetes, metabolic syndrome and obesity : targets and therapy · 2020Article
- Combining Host Genetics and Functional Analysis to Depict Inflammasome Contribution in Tuberculosis Susceptibility and Outcome in Endemic Areas.Frontiers in immunology · 2020Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundInflammasomes 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.
methodsThis 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.
resultsAmong 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 < .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], 67-345 mL; P = .004 and forced expiratory volume in 1 second, 143 mL higher; 95% CI, 11-274 mL; P = .034).
conclusionsA 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.
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