Circulating immune biomarkers indicate patients' immune imbalance and predict their disease severity and poor prognosis in pulmonary tuberculosis

A comprehensive understanding of the host immune response and identifying valuable markers to predict disease severity and patient's prognosis is a crucial issue.

Plasma levels of 12 soluble immune checkpoints (sICPs), 12 cytokines/chemokines and blood immune cell subsets were analyzed through flow cytometry.

Seven sICPs, such as sCD25 (P < 0.001), sCD27 (P < 0.001), sPD-L1 (P < 0.001), sPD-L2 (P = 0.031), sTim-3 (P < 0.001), sLAG-3 (P = 0.003), sGal-9 (P < 0.001) were positively correlated with disease severity in pulmonary tuberculosis (PTB) patients (n = 78). Four cytokines/chemokines, such as IL-6 (P < 0.001), IL-8 (P < 0.01), IP-10 (P < 0.001) and IFN-γ (P < 0.01), and some routine laboratory examinations, such as absolute neutrophil count (Neutrophil, P < 0.001), were also significantly elevated in severe PTB (SE). However, absolute lymphocyte count (LY, P < 0.001) was significantly lower in SE patients. Through Lasso regression analysis, six factors, including sCD25,sTim-3,IP-10, LY, Neutrophil, lactic dehydrogenase (LDH) were screened and weighted to form the Immune Imbalance Score (IIS). Patients with higher IIS had higher possibility to experience severe illness (P < 0.001) and shorter survival time (P < 0.001). Furthermore, the result of blood immune cell revealed that the frequencies of exhausted CD8 + T cells (Tim-3 + CD8+T cells, n = 48, P = 0.037) were significantly increased in SE patients than those in non-SE patients.

Patients with severe PTB exhibited a high inflammatory status, but their lymphocytes decreased and CD8 + T cells showed exhaustion. Patients' IIS could potentially serve as biomarkers to predict PTB patients' disease severity and prognosis.