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Tytuł pozycji:

Blood signatures for second stage human African trypanosomiasis: a transcriptomic approach.

Tytuł :
Blood signatures for second stage human African trypanosomiasis: a transcriptomic approach.
Autorzy :
Mulindwa J; Department of Biochemistry and Sports Sciences, College of Natural Sciences, Makerere University, P. O. Box 7062, Kampala, Uganda. .
Matovu E; Department of Biotechnical and Diagnostic Sciences, College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, P. O. Box 7062, Kampala, Uganda.
Enyaru J; Department of Biochemistry and Sports Sciences, College of Natural Sciences, Makerere University, P. O. Box 7062, Kampala, Uganda.
Clayton C; Centre for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120, Heidelberg, Germany.
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Źródło :
BMC medical genomics [BMC Med Genomics] 2020 Jan 30; Vol. 13 (1), pp. 14. Date of Electronic Publication: 2020 Jan 30.
Typ publikacji :
Journal Article; Research Support, Non-U.S. Gov't
Język :
English
Imprint Name(s) :
Original Publication: London : BioMed Central
MeSH Terms :
RNA-Seq*
Transcriptome*
Trypanosoma brucei gambiense*
Trypanosomiasis, African*/blood
Trypanosomiasis, African*/cerebrospinal fluid
Up-Regulation*
Adolescent ; Adult ; Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Child ; Female ; Humans ; Male
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Grant Information :
H3A/18/004 United Kingdom WT_ Wellcome Trust
Contributed Indexing :
Keywords: Blood*; CSF*; Human African Trypanosomiasis*; Human host transcriptome*; T. b rhodesiense*
Substance Nomenclature :
0 (Biomarkers)
Entry Date(s) :
Date Created: 20200201 Date Completed: 20201216 Latest Revision: 20201216
Update Code :
20210210
PubMed Central ID :
PMC6993467
DOI :
10.1186/s12920-020-0666-5
PMID :
32000760
Czasopismo naukowe
Background: Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient's immune response in the early and late stages of the disease.
Methods: RNASeq was carried out on blood and cerebral spinal fluid (CSF) samples obtained from T. b. rhodesiense infected patients. The control samples used were from healthy individuals in the same foci. The Illumina sequenced reads were analysed using the Tuxedo suite pipeline (Tophat, Cufflinks, Cuffmerge, Cuffdiff) and differential expression analysis carried out using the R package DESeq2. The gene enrichment and function annotation analysis were done using the ToppCluster, DAVID and InnateDB algorithms.
Results: We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n = 3) and late stage CSF (n = 3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n = 3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log 2 FC > 2.5) in both the blood and CSF.
Conclusion: The data yields insights into the host's response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.
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