Whole blood RNA signatures in leprosy patients identify reversal reactions before clinical onset: a prospective, multicenter study
| Autor: | Sayera Banu, Jolien J. van der Ploeg-van Schip, Yonas Bekele, Robert L. Modlin, Abraham Aseffa, Mariëlle C. Haks, Saraswoti Khadge, Annemieke Geluk, Pratibha Thapa, Chhatra B. Kunwar, Maria Tió-Coma, Milton Ozório Moraes, Jelle J. Goeman, Erik W. van Zwet, Isabela Maria Bernardes Goulart, Rosane M. B. Teles, Kidist Bobosha, Roberta Olmo Pinheiro, Deanna A. Hagge, Anouk van Hooij, Tom H. M. Ottenhoff |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent 030231 tropical medicine lcsh:Medicine Disease Predictive markers Disease cluster Clinical onset Article Transcriptome Young Adult 03 medical and health sciences 0302 clinical medicine Nepal Leprosy medicine Humans Prospective Studies lcsh:Science Mycobacterium leprae Netherlands Whole blood Bangladesh Multidisciplinary biology business.industry lcsh:R Prognosis medicine.disease biology.organism_classification 030104 developmental biology Multicenter study Immunology Female lcsh:Q Ethiopia business Biomarkers Brazil |
| Zdroj: | Scientific Reports, 9 Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-54213-y |
| Popis: | Early diagnosis of leprosy is challenging, particularly its inflammatory reactions, the major cause of irreversible neuropathy in leprosy. Current diagnostics cannot identify which patients are at risk of developing reactions. This study assessed blood RNA expression levels as potential biomarkers for leprosy. Prospective cohorts of newly diagnosed leprosy patients, including reactions, and healthy controls were recruited in Bangladesh, Brazil, Ethiopia and Nepal. RNA expression in 1,090 whole blood samples was determined for 103 target genes for innate and adaptive immune profiling by dual color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification (dcRT-MLPA) followed by cluster analysis. We identified transcriptomic biomarkers associated with leprosy disease, different leprosy phenotypes as well as high exposure to Mycobacterium leprae which respectively allow improved diagnosis and classification of leprosy patients and detection of infection. Importantly, a transcriptomic signature of risk for reversal reactions consisting of five genes (CCL2, CD8A, IL2, IL15 and MARCO) was identified based on cross-sectional comparison of RNA expression. In addition, intra-individual longitudinal analyses of leprosy patients before, during and after treatment of reversal reactions, indicated that several IFN-induced genes increased significantly at onset of reaction whereas IL15 decreased. This multi-site study, situated in four leprosy endemic areas, demonstrates the potential of host transcriptomic biomarkers as correlates of risk for leprosy. Importantly, a prospective five-gene signature for reversal reactions could predict reversal reactions at least 2 weeks before onset. Thus, transcriptomic biomarkers provide promise for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|