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The diagnostic value and validation of IL-22 combimed with sCD40L in tuberculosis pleural effusion
Yuzhen Xu1, Jing Wu1, Qiuju Yao2
1Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Medical College, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, People's Republic of China.
Insights
Cytokine levels in pleural effusion can distinguish tuberculosis pleurisy from malignant pleurisy. Interleukin-22 (IL-22) and soluble CD40 ligand (sCD40L) show high accuracy in diagnosing tuberculosis pleurisy.
Area of Science:
- Immunology
- Respiratory Medicine
- Infectious Diseases
Background:
- Cytokines are implicated in tuberculosis immune defense.
- Distinguishing tuberculosis pleurisy from malignant pleurisy is clinically important.
- Pleural effusion analysis is key for differential diagnosis.
Purpose of the Study:
- To evaluate cytokine levels in pleural effusion for differential diagnosis.
- To identify specific cytokines that can differentiate tuberculosis pleurisy from malignant pleurisy.
- To establish diagnostic thresholds for key cytokines.
Main Methods:
- Multiplex cytokine assay used to measure 14 cytokines in pleural effusion.
- Analysis included training (n=82) and validation (n=76) cohorts.
- Receiver operating characteristic (ROC) curve analysis determined threshold values.
Main Results:
- All 14 cytokines were significantly higher in tuberculosis pleurisy compared to malignant pleurisy (P < 0.05).
- IL-22, sCD40L, IFN-γ, TNF-α, and IL-31 showed high diagnostic accuracy (AUC ≥ 0.920).
- Combined IL-22 and sCD40L achieved 94.0% sensitivity and 96.9% specificity in the training cohort, validated in the validation cohort.
Conclusions:
- Elevated cytokine levels in pleural effusion differentiate tuberculosis pleurisy from malignant pleurisy.
- Specific thresholds for IL-22 (≥ 18.87 pg/mL) and sCD40L (≥ 53.08 pg/mL) offer an efficient diagnostic strategy.
- This cytokine-based approach provides a valuable tool for clinical diagnosis.
Background:
There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy.
Methods:
A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort.
Results:
The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort.
Conclusion:
We demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy.
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