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| Autor | Krishnan, Sonya | pt_BR |
| Autor | Queiroz, Artur Trancoso Lopo de | pt_BR |
| Autor | Gupta, Amita | pt_BR |
| Autor | Gupte, Nikhil | pt_BR |
| Autor | Bisson, Gregory P. | pt_BR |
| Autor | Kumwenda, Johnstone | pt_BR |
| Autor | Naidoo, Kogieleum | pt_BR |
| Autor | Mohapi, Lerato | pt_BR |
| Autor | Mave, Vidya | pt_BR |
| Autor | Mngqibisa, Rosie | pt_BR |
| Autor | Lama, Javier R. | pt_BR |
| Autor | Hosseinipour, Mina C. | pt_BR |
| Autor | Andrade, Bruno de Bezerril | pt_BR |
| Autor | Karakousis, Petros C. | pt_BR |
| Fecha de acceso | 2021-07-08T18:52:20Z | |
| Fecha de disponibilización | 2021-07-08T18:52:20Z | |
| Fecha de publicación | 2021 | |
| Referencia | KRISHNAN, Sonya et al. Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV. Frontiers in Immunology, p. 1-10, 8 June 2021. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/48078 | |
| Promoción | National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701 | pt_BR |
| Promoción | Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU) (NIH/NIAID UM1AI069465) | pt_BR |
| Promoción | AIDS Clinical Trials Group (ACTG) and CRDF Global | pt_BR |
| Promoción | Johns Hopkins University Center for AIDS Research (P30AI094189) | pt_BR |
| Promoción | National Institute of Health T32 AI007291-27 | pt_BR |
| Promoción | NIH/NIAID grant K24AI143447 | pt_BR |
| Idioma | eng | pt_BR |
| Editor | Frontiers Media | pt_BR |
| Derechos de autor | open access | pt_BR |
| Palabras clave en Portugués | Tuberculose | pt_BR |
| Palabras clave en Portugués | HIV | pt_BR |
| Palabras clave en Portugués | MicroRNAs | pt_BR |
| Palabras clave en Portugués | Metabolômica | pt_BR |
| Palabras clave en Portugués | Biomarcadores | pt_BR |
| Título | Integrative multi-omics reveals serum markers of tuberculosis in advanced HIV | en |
| Tipo del documento | Article | pt_BR |
| DOI | 10.3389/fimmu.2021.676980 | pt_BR |
| Resumen en Inglés | Tuberculosis (TB) accounts for disproportionate morbidity and mortality among persons living with HIV (PLWH). Conventional methods of TB diagnosis, including smear microscopy and Xpert MTB/RIF, have lower sensitivity in PLWH. Novel high-throughput approaches, such as miRNAomics and metabolomics, may advance our ability to recognize subclinical and difficult-to-diagnose TB, especially in very advanced HIV. We conducted a case-control study leveraging REMEMBER, a multi-country, open-label randomized controlled trial comparing 4-drug empiric standard TB treatment with isoniazid preventive therapy in PLWH initiating antiretroviral therapy (ART) with CD4 cell counts <50 cells/mL. Twenty-three cases of incident TB were site-matched with 32 controls to identify microRNAs (miRNAs), metabolites, and cytokines/chemokines, associated with the development of newly diagnosed TB in PLWH. Differentially expressed miRNA analysis revealed 11 altered miRNAs with a fold change higher than 1.4 or lower than -1.4 in cases relative to controls (p<0.05). Our analysis revealed no differentially abundant metabolites between cases and controls. We found higher TNFa and IP-10/CXCL10 in cases (p=0.011, p=0.0005), and higher MDC/CCL22 in controls (p=0.0072). A decision-tree algorithm identified gamma-glutamylthreonine and hsa-miR215-5p as the optimal variables to classify incident TB cases (AUC 0.965; 95% CI 0.925-1.000). hsa-miR-215-5p, which targets genes in the TGF-b signaling pathway, was downregulated in cases. Gamma-glutamylthreonine, a breakdown product of protein catabolism, was less abundant in cases. To our knowledge, this is one of the first uses of a multi-omics approach to identify incident TB in severely immunosuppressed PLWH. | en |
| Afiliación | Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States. | pt_BR |
| Afiliación | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research. Salvador, BA, Brasil. | pt_BR |
| Afiliación | Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India / Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, United States. | pt_BR |
| Afiliación | Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
| Afiliación | University of Pennsylvania. Perelman School of Medicine. Department of Medicine. Division of Infectious Diseases. Philadelphia, PA, United States. | pt_BR |
| Afiliación | College of Medicine-Johns Hopkins Project. Blantyre, Malawi. | pt_BR |
| Afiliación | University of KwaZulu-Natal. Centre for the AIDS Programme of Research in South Africa. Nelson R. Mandela School of Medicine. College of Health Sciences. Durban, South Africa / University of KwaZulu-Natal. Doris Duke Medical Research Institute. South African Medical Research Council Pathogenesis and Treatment Research Unit. Durban, South Africa. | pt_BR |
| Afiliación | University of the Witwatersrand. Perinatal HIV Research Unit. Johannesburg, South Africa. | pt_BR |
| Afiliación | Johns Hopkins University Clinical Research Site. Byramjee Jeejeebhoy Government Medical College. Pune, India. | pt_BR |
| Afiliación | Enhancing Care Foundation. Durban International Clinical Research Site. Durban, South Africa. | pt_BR |
| Afiliación | Asociacion Civil Impacta Salud y Educacion. Lima, Peru. | pt_BR |
| Afiliación | University of North Carolina. Project-Malawi. Lilongwe, Malawi / University of North Carolina. Department of Medicine. Division of Infectious Diseases. Chapel Hill, NC, United States. | pt_BR |
| Afiliación | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Curso de Medicina. Salvador, BA, Brasil. | pt_BR |
| Afiliación | Johns Hopkins University School of Medicine. Center for Clinical Global Health Education and Center for Tuberculosis Research. Department of Medicine. Division of Infectious Diseases. Baltimore, MD, United States / Johns Hopkins Bloomberg School of Public Health. Department of International Health. Baltimore, MD, United States. | pt_BR |
| Palavras clave en Inglês | Tuberculosis | en |
| Palavras clave en Inglês | HIV | en |
| Palavras clave en Inglês | MicroRNA | en |
| Palavras clave en Inglês | Metabolomics | en |
| Palavras clave en Inglês | Biomarker | en |
| Palavras clave en Inglês | Multi-omics | pt_BR |
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