Abstract:

Objective: To evaluate the auxiliary diagnostic value of detecting Mycobacterium tuberculosis (MTB)-specific cytokines (interferon-γ (IFN-γ) and interleukin-2 (IL-2)) combined with common laboratory indicators in extrapulmonary tuberculosis. Methods: A prospective study was conducted. A total of 158 inpatients with extrapulmonary tuberculosis who were treated at Xi'an Chest Hospital from August 2023 to September 2024 were consecutively included as the extrapulmonary tuberculosis group; 107 inpatients with non-tuberculous extrapulmonary diseases treated at Xi'an Chest Hospital during the same period were selected as the control group. All subjects underwent MTB-specific dual-factor detection, mycobacterium culture, real-time fluorescent quantitative PCR (qRT-PCR), real-time fluorescent RNA isothermal detection (SAT-TB), MTB nucleic acid detection (isothermal amplification DNA), GeneXpert MTB/RIF detection (referred to as “Xpert”), and acid-fast bacilli smear microscopy. Additionally, procalcitonin (PCT), C-reactive protein (CRP), systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) were tested. The auxiliary diagnostic value of MTB-specific dual factors alone and in combination with common laboratory indicators (PCT, CRP, SII, NLR, and PLR) for extrapulmonary tuberculosis was evaluated. Results: With clinical diagnosis as the reference standard, the sensitivity, specificity, positive predictive value, and negative predictive value of MTB-specific dual-factor detection were 78.48% (124/158), 71.96% (77/107), 80.52% (124/154), and 69.37% (77/111), respectively. The sensitivity was higher than that of the other 6 methods. Both the Youden index (0.504) and the consistency test Kappa value (0.501) were higher than those of the other 6 detection methods. In the methodological comparison, the positive detection rate of the serological group (MTB-specific dual factors) was 78.48% (124/158), which was significantly higher than that of the molecular biology group (qRT-PCR, SAT-TB, Xpert, and isothermal amplification DNA) and the bacteriology group (mycobacterium culture and acid-fast bacilli smear microscopy), with positive rates of 39.87% (63/158) and 26.58% (42/158), respectively. The differences were statistically significant (χ²=48.743 and 85.333, both P<0.001). In the comparison of laboratory indicators, the levels of PCT, CRP, SII, and PLR in the extrapulmonary tuberculosis group were 0.00 (0.00, 0.09) pg/ml, 24.08 (3.56, 71.69) mg/L, 976.76 (571.92, 2159.82), and 190.66 (135.02, 267.31), respectively; in the control group, the levels were 0.06 (0.00, 0.18)pg/ml, 10.05 (0.39, 63.44) mg/L, 784.56 (401.14, 1409.55), and 151.54 (108.23, 218.47), respectively. The differences between the two groups were statistically significant (U=-2.592, -2.024, -2.484, and -3.285; P=0.010, 0.043, 0.013, and 0.001, respectively). The results of the receiver operating characteristic curve showed that the area under the curve for the detection of MTB-specific dual factors combined with common laboratory indicators (PCT, CRP, SII, NLR, and PLR) was 0.801 (95%CI: 0.720-0.881). Conclusion: MTB-specific dual-factor detection has good sensitivity in the diagnosis of extrapulmonary tuberculosis, and combining it with common laboratory indicators (PCT, CRP, SII, NLR, and PLR) can improve the diagnostic accuracy of extrapulmonary tuberculosis.

Key words: Mycobacterium tuberculosis, Interferons, Interleukin-2, Diagnosis, differential, Extrapulmonary tuberculosis