Host Response to Infection by Direct Analysis of Leukocyte Single Cell-type Gene Expression/transcript Abundance, Direct LS-TA

The Chinese University of Hong Kong

Status: Active, not recruiting

Conditions: Infection; Viral Diseases; Gene Expression; Active Tuberculosis; Gene Expression Profiling; Bacterial Infections

Treatments: Other: No intervention

Study type: Observational

Funder types: Other

Identifiers

NCT06838780

Direct LS-TA retrospective

Details and patient eligibility

About

Febrile illness is a common condition, particularly among young patients and it is crucial to have an early triage of patients according to various aetiologies to enable appropriate treatment. Most diagnostic tests are targeted towards the detection of pathogens while other assays are mostly related to serum proteins. Blood cells transcriptome has been explored to differentiate bacterial and viral infections.

Here, we propose to develop a rapid test using the host responses in terms of gene expressions of single-cell populations of peripheral leukocytes (monocytes and granulocytes) to differentiate three major categories of infections that are bacterial, viral, and tuberculosis.

The assay is called Direct leukocyte single cell-type transcript abundance (TA) assay (DIRECT LS-TA) as it can directly determine the gene expression of a specified single cell-type (e.g. monocytes and granulocytes) among various leukocyte cell populations directly in a peripheral blood sample. Such results signify the nature of host response and can be used to indicate the type of infection (viral, bacterial or active tuberculosis).

Full description

DIRECT LS-TA is a ratio-based biomarker (RBB) for blood gene expression analysis which can be performed in commonly available equipments (e.g. qPCR or digital PCR machines). Using the ratio of TA of prior defined numerator gene and denominator gene, this RBB can quantify gene expression of the specified constitutional single cell-type (e.g. monocytes and granulocytes) inside a cell-mixture sample of Whole blood.

DIRECT LS-TA was a method pioneered by the PI [Tang 2017, https://patents.google.com/patent/US9589099B2/]. And it has been developed for quantification of early B cell response after vaccination [DOI: 10.3390/genes12070971].

Recently, the method is used to develop host response biomarkers after infection to differentiate the type of pathogens (such as viral, bacterial or active tuberculosis). Numerator and denominator genes have been identified by using public gene expression datasets for monocytes and granulocytes. Diagnostic performance was good using these public data.

Therefore, these RBBs will be applied in these retrospective samples to evaluate and compare their diagnostic (triage) performance of febrile patients into different pathogen etiologies.

Enrollment: 192 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Bacterial infection sample: positive isolation of organism in blood culture (Bacterial infection sample group)
• Clinical diagnosed active TB (Tuberculosis infection group)

Exclusion criteria

• End stage renal failure
• Pregnancy
• Infections for which long term antibiotic treatment is strongly recommended (including infective endocarditis, osteoarticular infections, cerebral or hepatic or lung abscesses, tuberculosis or nontuberculous mycobacterial infections)

Trial design

192 participants in 3 patient groups

Vaccination Controls

Description:

Up to 200 adult samples collected as the baseline of this study will be used to establish the reference ranges of the ratio-based biomarkers by quantitative PCR or digital PCR.

Treatment:

Other: No intervention

Bacterial infection samples

Description:

A retrospective sample of adult patients with positive bacterial blood culture.

Treatment:

Other: No intervention

Tuberculosis samples

Description:

A retrospective sample of adult patients who were diagnosed to have active tuberculosis disease.

Treatment:

Other: No intervention