Differential gene expression of activating Fcγ receptor classifies active tuberculosis regardless of human immunodeficiency virus status or ethnicity

New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targ...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:Clinical microbiology and infection Ročník 20; číslo 4; s. O230 - O238
Hlavní autoři: Sutherland, J.S., Loxton, A.G., Haks, M.C., Kassa, D., Ambrose, L., Lee, J.-S., Ran, L., van Baarle, D., Maertzdorf, J., Howe, R., Mayanja-Kizza, H., Boom, W.H., Thiel, B.A., Crampin, A.C., Hanekom, W., Ota, M.O.C., Dockrell, H., Walzl, G., Kaufmann, S.H.E., Ottenhoff, T.H.M.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Elsevier Ltd 01.04.2014
Témata:
Adolescent
Adult
Africa South of the Sahara
Biomarkers - blood
Biosignature
Blood
Ethnicity
Female
Gene Expression
Gene Expression Profiling
HIV Infections - complications
Human immunodeficiency virus
Humans
Lentivirus
Male
Middle Aged
Mycobacterium
Receptors, IgG - blood
Retroviridae
RT-MLPA
tuberculosis
Tuberculosis - diagnosis
Young Adult
Africa South of the Sahara
gene expression
tuberculosis
Biosignature
RT-MLPA
ISSN:1198-743X, 1469-0691, 1469-0691
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:New diagnostics and vaccines for tuberculosis (TB) are urgently needed, but require an understanding of the requirements for protection from/susceptibility to TB. Previous studies have used unbiased approaches to determine gene signatures in single-site populations. The present study utilized a targeted approach, reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), to validate these genes in a multisite study. We analysed ex vivo whole blood RNA from a total of 523 participants across four sub-Saharan countries (Ethiopia, Malawi, South Africa, and The Gambia) with differences in TB and human immunodeficiency virus (HIV) status. We found a number of genes that were expressed at significantly lower levels in participants with active disease than in those with latent TB infection (LTBI), with restoration following successful TB treatment. The most consistent classifier of active disease was FCGR1A (high-affinity IgG Fc receptor 1 (CD64)), which was the only marker expressed at significantly higher levels in participants with active TB than in those with LTBI before treatment regardless of HIV status or genetic background. This is the first study to identify a biomarker for TB that is not affected by HIV status or geo-genetic differences. These data provide valuable clues for understanding TB pathogenesis, and also provide a proof-of-concept for the use of RT-MLPA in rapid and inexpensive validation of unbiased gene expression findings.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1198-743X
1469-0691
1469-0691
DOI:10.1111/1469-0691.12383