The diagnostic value of CD101 in smear-negative pulmonary tuberculosis

Unlike smear-positive tuberculosis (TB) which is more easily diagnosed due to the presence of Mycobacterium tuberculosis (MTB) in sputum, smear-negative pulmonary tuberculosis (SN-TB) poses a diagnostic challenge that can lead to delayed treatment hence new molecular diagnostic markers are urgently needed. The aim of this study was to analyze the expression of CD101 in peripheral blood mononuclear cells (PBMCs), T cells and natural killer (NK) cells of patients with SN-TB through a case-control study and to assess the value of CD101 alone or combined with other cytokines in the auxiliary diagnosis of SN-TB.

Sixty-three newly treated patients with TB and negative smear results diagnosis by clinicians were included as the SN-TB group, while 59 healthy individuals [healthy control (HC)] were included as the control group. The expression of CD101 in PBMCs of the two groups was detected via real-time quantitative polymerase chain reaction (RT-qPCR). The expression of CD101 on T cells and NK cells, as well as the expression of T helper (Th) 1/2/17-related cytokines was detected by flow cytometry. Spearman analysis was used to analyze the correlation between CD101 expression, cytokines and clinical indicators in patients with SN-TB. Receiver operating characteristic (ROC) curve analysis was used to analyze the sensitivity and specificity of CD101 alone or in combination with other cytokines in diagnosing SN-TB.

Compared with the control group, the experimental group showed high CD101 expression in PBMCs and CD4⁺ T cells but not in CD8⁺ T cells or NK cells. Th1/Th2-related cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were highly expressed in patients with SN-TB, but there was no significant difference in the expression of the Th17-related cytokine (IL-17A). The expression of CD101 on CD4⁺ T cells in patients with SN-TB was positively correlated with cytokines IL-2 and IFN-γ and the clinical indicators of ESR and CRP. CD101 on CD4⁺ T cells could well distinguish patients with SN-TB from HC, with a sensitivity of 71.43%, a specificity of 71.19% and an area under the curve (AUC) of 0.7604. The sensitivity of CD101⁺CD4⁺ (%) combined with IL-2 was 73.25%, the specificity was 68.25% and the AUC was 0.7893. The sensitivity of CD101⁺CD4⁺ (%) combined with IFN-γ was 72.88%, the specificity was 66.67% and the AUC was 0.7678. The sensitivity of CD101⁺CD4⁺ (%) combined with IFN-γ and IL-2 was 74.58%, the specificity was 74.60% and the AUC was 0.7899.

The expression of CD101 on CD4⁺ T cells could distinguish patients with SN-TB from healthy individuals and was correlated with key TB infection cytokines, including IL-2 and IFN-γ, as well as with ESR and CRP. CD101 demonstrated good diagnostic efficacy in combination with cytokines. It might thus be an indicator for laboratory-assisted diagnosis of SN-TB.