Plasma immune profiling combined with machine learning contributes to diagnosis and prognosis of active pulmonary tuberculosis.

Tuberculosis (TB) remains one of the deadliest chronic infectious diseases globally. Early diagnosis not only prevents the spread of TB but also ensures effective treatment. However, the absence of non-sputum-based diagnostic tests often leads to delayed TB diagnoses. Inflammation is a hallmark of TB, we aimed to identify biomarkers associated with TB based on immune profiling. We collected 222 plasma samples from healthy controls (HCs), disease controls (non-TB pneumonia; PN), patients with TB (TB), and cured TB cases (RxTB). A high-throughput protein detection technology, multiplex proximity extension assays (PEA), was applied to measure the levels of 92 immune proteins. Based on differential analysis and the correlation with TB severity, we selected 9 biomarkers (CXCL9, PDL1, CDCP1, CCL28, CCL23, CCL19, MMP1, IFNγ and TRANCE) and explored their diagnostic capabilities through 7 machine learning methods. We identified combination of these 9 biomarkers that distinguish TB cases from controls with an area under the receiver operating characteristic curve (AUROC) of 0.89-0.99, with a sensitivity of 82-93% at a specificity of 88-92%. Moreover, the model excels in distinguishing severe TB cases, achieving AUROC exceeding 0.95, sensitivities and specificities exceeding 93.3%. In summary, utilizing targeted proteomics and machine learning, we identified a 9 plasma proteins signature that demonstrates significant potential for accurate TB diagnosis and clinical outcome prediction.