关键词: 重症肺结核, γ-干扰素释放试验, FadD9重组蛋白, 诊断, 死亡预后, 预测价值

Abstract: Objective To analyze the value of interferon-gamma release assay（IGRA）combined with FadD9 recombinant protein in the diagnosis and prognosis of severe pulmonary tuberculosis（SPT）. Methods 127 and 74 patients treated in our hospital from January 2018 to February 2021 were included in the SPT and non-SPT groups. Besides,36 patients with more than one year of close contact with tuberculosis patients were assigned into the close contact group, and 92 healthy subjects into the control group during the same period in our hospital. The fadD9 gene sequence（gene ID：888574）was obtained from the website of the National Biotechnology Information Center of the United States,and the recombinant FadD9 protein was prepared,with its immunogenicity,specific antibody level and cellular immunity in clinical plasma samples evaluated. Based on the prognosis of SPT patients we recorded and counted,the patients were divided into the survival group（n=93） and the death group（n=34）,and the general clinical data of the two groups were compared. The risk factors affecting the death of patients with SPT were screened by Cox proportional hazard regression,the Nomogram prediction model was established, and the consistency index（C-index）was calculated. The ROC,calibration curve and clinical decision curve were used to evaluate the differentiation,calibration and clinical effectiveness of the Nomogram prediction model.Results Similar to the positive reference antigen Ag85A protein,the A value of FadD9 recombinant protein was higher than that of the negative control group. The serum antibody titer of the recombinant FadD9 protein was 1∶12 800. The levels of IL-2,TNF- α and IFN- γ in FadD9 immunized group were 126.95,225.87 and 395.92 pg/mL,respectively. The level of anti-FadD9 antibody in the SPT group was significantly higher than that in the close group and control group,the difference being statistically significant（P<0.001）. BMI,APACHE Ⅱ,COPD,pulmonary infection,respiratory failure,cor pulmonale,organ damage,multidrug resistant tuberculosis,hypoalbuminemia,IGRA and FadD9 recombinant protein antibody levels were independent risk factors for death in SPT patients（P<0.05）. The C-index of the constructed Nomogram model was 0.742（95% CI：0.684~0.845）,the AUC of the Nomogram model was 0.802（95% CI：0.764~0.840）,and the sensitivity,specificity and Yoden index were 85.42%,74.05% and 0.595. On the whole,the accuracy and effectiveness of Nomogram model in predicting the death of SPT patients were found to be satisfactory. The area under the curve of FadD9 recombinant protein for the diagnosis of severe pulmonary tuberculosis was 0.748, the best critical value was 0.352,the sensitivity was 97.33%, and the specificity was 72.51%.Conclusion IGRA seems to be effective in the diagnosis of SPT,with FadD9 recombinant protein serving as a candidate component of a new antigen combination of IGRA,which has high sensitivity in the diagnosis of SPT. To some extent,the Nomogram model constructed in this study could be used as an auxiliary tool for predicting the prognosis of death in SPT patients.

Key words: Severe pulmonary tuberculosis, IGRA, FadD9 recombinant protein, Diagnosis, Death prognosis, Predictive value