CD38+CD27-TNF-α + on Mtb-specific CD4+ T Cells Is a Robust Biomarker for Tuberculosis Diagnosis

Area of Science:

• Immunology
• Infectious Diseases
• Biomarker Discovery

Background:

• Tuberculosis (TB) diagnosis relies heavily on detecting Mycobacterium tuberculosis (Mtb) bacilli, which is challenging.
• Mtb-specific immune responses, including cytokine production, offer alternative diagnostic avenues.
• Identifying active TB from latent infection requires precise host immune markers.

Purpose of the Study:

• To evaluate phenotypic markers on Mtb-specific cytokine-producing immune cells for active TB diagnosis.
• To identify a robust host immune biomarker for distinguishing active TB from other conditions.
• To assess the biomarker's ability to differentiate treatment-naive TB from cured TB.

Main Methods:

• Recruited subjects with pulmonary TB, extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls.
• Employed polychromatic flow cytometry on peripheral blood mononuclear cells to identify immune biomarkers.
• Validated biomarker performance using whole blood in a separate cohort.

Main Results:

• A specific subset of Mtb-specific CD4+ T cells (CD38+CD27-) secreting cytokines effectively distinguished active TB.
• Tumor necrosis factor-α (TNF-α) secretion from CD38+CD27-CD4+ T cells showed high diagnostic accuracy (96.15% specificity, 90.16% sensitivity in validation).
• This T-cell subset also differentiated between treatment-naive TB patients and those cured of TB.

Conclusions:

• The Mtb-specific CD38+CD27-TNF-α+CD4+ T-cell subset is a reliable biomarker for TB diagnosis.
• This biomarker can also be used to assess the cure of tuberculosis following treatment.
• This discovery provides a promising new tool for managing TB globally.