Biomarkers Can Identify Pulmonary Tuberculosis in HIV-infected Drug Users Months Prior to Clinical Diagnosis
| Autor: | Mariëlle C. Haks, Martien W. Borgdorff, Tom H. M. Ottenhoff, Simone A. Joosten, Rosa Sloot, Erik W. van Zwet, Maarten F. Schim van der Loeff, Maarten Scholing, Sytze T. Keizer |
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| Přispěvatelé: | Epidemiology and Data Science, Infectious diseases, AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology dcRT-MLPA lcsh:Medicine HIV Infections Bioinformatics Pathogenesis 0302 clinical medicine Hiv infected Medicine 030212 general & internal medicine media_common lcsh:R5-920 0303 health sciences education.field_of_study Interleukin-13 General Medicine Middle Aged 3. Good health Interferon Type I Host biomarkers Female Original Article lcsh:Medicine (General) Adult Drug medicine.medical_specialty Tuberculosis Substance-Related Disorders media_common.quotation_subject Population General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Pulmonary tuberculosis Internal medicine Humans education Tuberculosis Pulmonary Retrospective Studies 030304 developmental biology business.industry lcsh:R HIV Retrospective cohort study medicine.disease Clinical diagnosis Gene expression business Biomarkers Transcription Factors |
| Zdroj: | EBioMedicine, 2(2), 172-179. Elsevier BV EBioMedicine EBioMedicine, Vol 2, Iss 2, Pp 172-179 (2015) |
| ISSN: | 2352-3964 |
| Popis: | Background Current diagnostic tests cannot identify which infected individuals are at risk for progression to tuberculosis (TB). Our aim was to identify biomarkers which can predict the development of TB prior to clinical diagnosis. Method In a retrospective case–control study, RNA of 14 HIV-infected drug users obtained before TB diagnosis (cases) and of 15 who did not develop TB (controls) was analyzed for the expression of 141 genes by dcRT-MLPA followed by Lasso regression analysis. Findings A combined analysis of IL13 and AIRE had the highest discriminatory power to identify cases up to 8 months prior to clinical diagnosis. Cases expressing IL13 had a gene expression pattern strongly enriched for type I IFN related signaling genes, suggesting that these genes represent processes that contribute to TB pathogenesis. Interpretation We here demonstrated that biomarkers, such as IL13-AIRE, can identify individuals that progress to TB within a high risk population, months prior to clinical diagnosis. Highlights • A predictive signature was detected in ex vivo PBMCs of HIV-infected drug users up to 8 months prior to clinical TB diagnosis; • Combined expression of IL13 and AIRE had the highest discriminatory power to identify cases months prior to TB diagnosis. • Cases expressing IL13 had a gene expression pattern that was strongly enriched for type I IFN related signalling genes. |
| Databáze: | OpenAIRE |
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