Research ArticleOriginal Article
Open Access

Retrospective analysis of the clinical utility of multi-cytokine profiles in smear-negative pulmonary tuberculosis

Xuemei Li, Weidong Zhao, Hong Han, Zhi Yang, Fengqing Bi and Yingchun He
Saudi Medical Journal July 2024, 45 (7) 658-666; DOI: https://doi.org/10.15537/smj.2024.45.7.20240310

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    - Diagnostic value of four cytokines alone or in combination for the smear-negative pulmonary tuberculosis. A) The receiver operating characteristic (ROC) curve of Interferons (IFN)-α, interleukin (IL)-2, IL-10, and IL-8. B) represents the ROC curve of the combination of IFN-α, IL-2, IL-10, and IL-8 for diagnosing smear-negative pulmonary tuberculosis. AUC: area under curve

Tables

  • Table 1

    - Demographic and clinical characteristics of TB and non-TB groups.

    CharacteristicsTB (n=77)Non-TB (n=48)P-value
    Age, median (IQR)53 (40, 64)59 (46, 67)0.266
    Gender, n (%)0.175
    Male48 (62.3%)24 (50.0%)
    Female29 (37.7%)24 (50.0%)
    BMI, mean ± SD20.11 ± 3.5323.46 ± 4.50<0.001
    WBC (×109/L), median (IQR)7.11 (5.42, 8.67)5.89 (4.64, 7.79)0.027
    Neutrophil (%), median (IQR)72.2 (66.0, 77.4)59.6 (50.1, 70.2)<0.001
    Monocyte (%), median (IQR)8.7 (6.6, 11.0)8.0 (6.3, 9.1)0.042
    ESR (mm/h), median (IQR)59 (21.5, 96.8)27.5 (12.0, 57.0)0.002
    CRP (ng/mL), median (IQR)29.21 (6.53, 59.46)3.26 (1.27, 21.00)<0.001
    IL-5, median (IQR)2.36 (1.41, 3.32)1.94 (1.58, 3.165)0.392
    IFN-a, median (IQR)1.40 (0.88, 2.06)1.22 (0.89, 1.63)0.161
    IL-2, median (IQR)1.41 (1.04, 1.85)1.18 (0.86, 1.52)0.027
    IL-6, median (IQR)12 (6.4, 25.46)3.01 (1.50, 4.94)<0.001
    IL-1b, median (IQR)5.17 (1.95, 10.26)3.25 (1.39, 8.10)0.087
    IL-10, median (IQR)1.68 (1.25, 4.09)1.39 (1.08, 2.31)0.079
    IFN-g, median (IQR)15.02 (5.47, 32.03)4.46 (1.99, 6.3)<0.001
    IL-8, median (IQR)6.44 (1.8, 26.19)4.05 (0.85, 9.34)0.023
    IL-17, median (IQR)2.68 (1.00, 7.20)2.72 (1.63, 13.02)0.195
    IL-4, median (IQR)1.36 (0.69, 1.90)1.19 (1.00, 1.62)0.471
    IL-12p70, median (IQR)1.36 (0.80, 1.85)1.48 (1.05, 1.87)0.575
    TNF-α, median (IQR)1.99 (1.09, 5.29)1.41 (0.82, 3.16)0.110
    IGRA positive, n (%)68 (88.3%)14 (29.2%)<0.001

    Chi-square for gender, t test for body mass index (BMI), Wilcoxon test for others. SD: standard deviation, IQR: interquartile, TB: tuberculosis, IL: interlukin, TNF-α: tumor necrosis factor-alpha, IGRA: interferon gamma release assay test, WBC: white blood cells, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein

    • Table 2

      - Demographic and clinical characteristics of smear-negative pulmonary tuberculosis (SNPT) and smear-positive pulmonary tuberculosis (SPPT) groups.

      CharacteristicsSNPT (n=42)SPPT (n=35)P-value
      Age, mean±standard deviation53.6 ± 14.750.7 ± 17. 90.432
      Gender, n (%)0.699
      Male27 (35.1%)21 (27.3%)
      Female15 (19.5%)14 (18.2%)
      BMI, median (IQR)20.4 (17.3, 22.1)18.9 (17.8, 22.5)0.943
      ESR (mm/h), median (IQR)42.5 (12.5, 95)70.5 (47.75, 99.75)0.091
      CRP (ng/mL), median (IQR)27.36 (5.87, 55.83)34.29 (9.95, 65.39)0.563
      WBC (×109/L), median (IQR)6.64 (5.09, 7.77)7.67 (6.57, 9.35)0.056
      Neutrophil (%), median (IQR)72.55 (65.2, 77.7)71.9 (66, 77.4)0.747
      Monocyte (%), mean ± SD8.7 ± 3.89.5 ± 3.20.319
      IL-5, median (IQR)2.83 (1.51, 4.22)2.09 (1.35, 2.83)0.104
      IFN-a, median (IQR)1.9 (1.09, 3.03)1.2 (0.74, 1.59)<0.001
      IL-2, median (IQR)1.66 (1.17, 2.44)1.22 (0.9, 1.48)0.012
      IL-6, median (IQR)11.44(6.44, 25.49)12.44 (6.06, 22.96)0.963
      IL-1b, median (IQR)7.86 (2.38, 13.9)3.32 (1.88, 5.71)0.032
      IL-10, median (IQR)2.17 (1.47, 4.6)1.53 (1.06, 1.88)0.005
      IFN-g, median (IQR)14.87 (7.44, 39.89)15.02 (3.84, 28.50)0.385
      IL-8, median (IQR)15.82 (1.99, 51.78)3 (1.00, 8.40)0.003
      IL-17, median (IQR)4.28 (1.44, 8.46)1.89 (0.89, 3.29)0.074
      IL-4, median (IQR)1.43 (0.64, 1.89)1.34 (0.87, 1.89)0.771
      IL-12P70, median (IQR)1.61 (0.92, 1.95)1.12 (0.74, 1.75)0.060
      TNF-a, median (IQR)2.81 (1.09, 5.66)1.7 (1.06, 3.51)0.231
      IGRA positive, n (%)34 (81.0%)34 (97.1%)0.015

      Chi-square test for gender and IGRA positive proportion, t test for age and monocyte, Wilcoxon test for others. BMI: body mass index, IQR: interquartile, IL: interlukin, TNF-α: tumor necrosis factor-alpha, IGRA: interferon gamma release assay test, WBC: white blood cells, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein

      • Table 3

        - Effect size of cytokine levels in smear-negative pulmonary tuberculosis (SNPT) and smear-positive pulmonary tuberculosis (SPPT) population.

        CharacteristicsSNPT (n=42)SPPT (n=35)Effect sizeP-value
        IL-5, median (IQR)2.83 (1.51, 4.22)2.09 (1.35, 2.83)0.35 (-0.11-0.80)0.104
        IFN-a, median (IQR)1.90 (1.09, 3.03)1.20 (0.74, 1.59)0.59 (0.13-1.05)<0.001
        IL-2, median (IQR)1.66 (1.17, 2.44)1.22 (0.90, 1.48)0.61 (0.15-1.07)0.012
        IL-6, median (IQR)11.44(6.44, 25.49)12.44 (6.06, 22.96)0.12 (-0.33-0.57)0.963
        IL-1b, median (IQR)7.86 (2.38, 13.9)3.32 (1.88, 5.71)0.37 (-0.08-0.83)0.032
        IL-10, median (IQR)2.17 (1.47, 4.6)1.53 (1.06, 1.88)0.62 (0.17-1.08)0.005
        IFN-g, median (IQR)14.87 (7.44, 39.89)15.02 (3.84, 28.50)0.19 (-0.26-0.64)0.385
        IL-8, median (IQR)15.82 (1.99, 51.78)3.00 (1.00, 8.40)0.76 (0.29-1.22)0.003
        IL-17, median (IQR)4.28 (1.44, 8.46)1.89 (0.89, 3.29)0.03 (-0.42-0.48)0.074
        IL-4, median (IQR)1.43 (0.64, 1.89)1.34 (0.87, 1.89)0.01 (-0.45-0.45)0.771
        IL-12P70, median (IQR)1.61 (0.92, 1.95)1.12 (0.74, 1.75)0.36 (-0.09-0.82)0.060
        TNF-a, median (IQR)2.81 (1.09, 5.66)1.70 (1.06, 3.51)-0.03 (-0.48-0.42)0.231
        IGRA positive, n (%)34 (81.0%)34 (97.1%)NA0.015

        NA: not analyzed. Effect sizes were calculated using the Cohen d. Absolute values of 0.20–0.49 represent a small change; values of 0.50–0.79 a medium change; and values of ≥0.80 a large change. IQR: interquartile, IL: interlukin, TNF-α: tumor necrosis factor-alpha, IGRA: interferon gamma release assay test, WBC: white blood cells

        • Table 4

          - Receiver operating characteristic analysis of cytokine levels in (SNPT) and smear-positive pulmonary tuberculosis (SPPT) population.

          CytokinesAUC (95%CI)Cut-offYouden valueP-valueSensitivitySpecificityPPVNPV
          IFN-a (pg/mL)0.734 (0.623-0.844)1.910.414<0.00191.4%50.0%87.5%60.4%
          IL-2 (pg/mL)0.668 (0.546-0.790)1.550.3670.00977.1%59.5%75.8%36.7%
          IL-10 (pg/mL)0.686 (0.564-0.809)2.060.405<0.00185.7%54.8%82.1%61.2%
          IL-8 (pg/mL)0.698 (0.580-0.816)9.460.395<0.00180.0%59.5%90.5%58.9%
          IFN-a+ IL-2+IL-10+IL-80.759 (0.652-0.865)-0.443<0.00180.0%64.2%79.4%65.1%

          CI: confidence interval, PPV: positive predictive value, NPV: negative predictive value, AUC: area under curve

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