A Two-Gene Signature for Tuberculosis Diagnosis in Persons With Advanced HIV

Background: Transcriptomic signatures for tuberculosis (TB) have been proposed and represent a promising diagnostic tool. Data remain limited in persons with advanced HIV. Methods: We enrolled 30 patients with advanced HIV (CD4 <100 cells/mm 3 ) in India; 16 with active TB and 14 without. Whole-b...

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Veröffentlicht in:Frontiers in immunology Jg. 12; S. 631165
Hauptverfasser: Kulkarni, Vandana, Queiroz, Artur T. L., Sangle, Shashi, Kagal, Anju, Salvi, Sonali, Gupta, Amita, Ellner, Jerrold, Kadam, Dileep, Rolla, Valeria C., Andrade, Bruno B., Salgame, Padmini, Mave, Vidya
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 22.02.2021
Schlagworte:
diagnosis
gene signature
HIV
Immunology
transcriptomics
tuberculosis
transcriptomics
diagnosis
HIV
gene signature
tuberculosis
ISSN:1664-3224, 1664-3224
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Zusammenfassung:Background: Transcriptomic signatures for tuberculosis (TB) have been proposed and represent a promising diagnostic tool. Data remain limited in persons with advanced HIV. Methods: We enrolled 30 patients with advanced HIV (CD4 <100 cells/mm 3 ) in India; 16 with active TB and 14 without. Whole-blood RNA sequencing was performed; these data were merged with a publicly available dataset from Uganda ( n = 33; 18 with TB and 15 without). Transcriptomic profiling and machine learning algorithms identified an optimal gene signature for TB classification. Receiver operating characteristic analysis was used to assess performance. Results: Among 565 differentially expressed genes identified for TB, 40 were shared across India and Uganda cohorts. Common upregulated pathways reflect Toll-like receptor cascades and neutrophil degranulation. The machine-learning decision-tree algorithm selected gene expression values from RAB20 and INSL3 as most informative for TB classification. The signature accurately classified TB in discovery cohorts (India AUC 0.95 and Uganda AUC 1.0; p < 0.001); accuracy was fair in external validation cohorts. Conclusions: Expression values of RAB20 and INSL3 genes in peripheral blood compose a biosignature that accurately classified TB status among patients with advanced HIV in two geographically distinct cohorts. The functional analysis suggests pathways previously reported in TB pathogenesis.
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This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology
Edited by: Novel N. Chegou, Stellenbosch University, South Africa
Reviewed by: Marielle C. Haks, Leiden University Medical Center, Netherlands; Jiezuan Yang, Zhejiang University, China
These authors have contributed equally to this work
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.631165