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QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases

F. Bartalesi, S. Vicidomini, D. Goletti, C. Fiorelli, G. Fiori, D. Melchiorre, E. Tortoli, A. Mantella, M. Benucci, E. Girardi, M. M. Cerinic, A. Bartoloni
European Respiratory Journal 2009 33: 586-593; DOI: 10.1183/09031936.00107608
F. Bartalesi
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S. Vicidomini
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D. Goletti
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C. Fiorelli
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G. Fiori
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D. Melchiorre
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E. Tortoli
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A. Mantella
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M. Benucci
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E. Girardi
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M. M. Cerinic
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A. Bartoloni
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  • Fig. 1—
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    Fig. 1—

    Flow diagram of the study population. QFT: QuantiFERON®-TB Gold in-tube (Cellestis Limited, Carnegie, Australia); TST: tuberculin skin testing; +: positive; -: negative.

Tables

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  • Table 1—

    Associations of demographic, epidemiological and clinical characteristics and therapy with QuantiFERON®-TB Gold in-tube (QFT-GIT)- and tuberculin skin test (TST)-positive results in subjects with rheumatic diseases: univariate analysis

    TotalQFT-GIT positivep-value#TST positivep-value#
    Total393 (100)52 (13.2)74 (18.8)
    Sex0.030.09
     Male137 (34.9)25 (18.2)32 (23.4)
     Female256 (65.1)27 (10.5)42 (16.4)
    BCG vaccinated0.10.009
     Yes16 (4.1)07 (9.5)
     No377 (95.9)52 (100.0)67 (90.5)
    Birth/residence in countries at high prevalence of TB0.70.05
     Yes18 (4.6)2 (3.8)7 (9.5)
     No375 (95.4)50 (96.2)67 (90.5)
    Age yrs0.0010.03
     ≤2945 (11.5)1 (2.2)2 (4.4)
     30–49129 (32.8)12 (9.3)25 (19.4)
     50–69167 (42.5)25 (15)35 (21.0)
     >7052 (13.2)14 (26.9)12 (23.1)
    Chest radiograph patterns0.080.009
     No lesions of past TB80 (20.3)6 (7.5)14 (17.5)
     Lesions of past TB41 (10.5)9 (22.0)15 (36.5)
     Other patterns272 (69.2)37 (13.5)45 (16.5)
    Close contact to patients with sputum-positive TB0.020.02
     Yes7 (1.8)3 (5.7)4 (5.4)
     No386 (98.2)49 (94.3)70 (94.6)
    Diagnosis0.30.4
     Rheumatoid arthritis201 (51.1)27 (13.4)35 (17.4)
     Psoriasic arthritis94 (23.9)23 (24.5)16 (17)
     Ankilosing spondilytis58 (14.8)5 (8.6)11 (19)
     Other¶40 (10.2)4 (10)5 (12.5)
    Therapy+
     No therapy in last 3 months83 (21.1)13 (25)22 (29.7)
     DMARDs75 (19.1)12 (23.1)0.919 (25.7)0.8
     DMARDs + steroids106 (27)13 (25)0.522 (29.7)0.3
     Steroids34 (8.7)2 (3.8)0.11 (1.3)0.004
     TNF-α inhibitors30 (7.6)6 (11.5)0.24 (5.4)0.1
     TNF-α inhibitors + DMARDs25 (6.4)4 (7.6)0.94 (5.4)0.2
     TNF-α inhibitors + steroids4 (1)00.300.2
     TNF-α inhibitors + DMARDs + steroids36 (9.2)2 (3.8)0.12 (2.7)0.009
    • Data are expressed as n (%), unless otherwise stated. BCG: bacillus Calmette–Guérin; TB: tuberculosis; DMARD: disease-modifying antirheumatic drugs; TNF-α: tumour necrosis factor-α. #: by Chi-squared test or Fisher's exact test as appropriate. ¶: includes uveitis, Crohn's disease, juvenile chronic arthritis, undifferentiated spondyloarthropathy (n = 3 for each); Behçet's disease, Still's disease, enteritis, temporal arteritis, scleroderma, seronegative oligoarthritis, seronegative spondyloarthritis, ulcerative colitis (n = 2 for each); systemic lupus erythematosus, systemic sclerosis, erythema nodosum, Wegener's granulomatosis, polymyalgia syndrome, sarcoidosis, reactive arthritis, psoriasis, myopathy of unclear origin, familial mediterranean fever, sacroileitis and seronegative spondyloarthritis with Castleman's disease (n = 1 for each). +: p-values were derived from comparison of the test results in patients with each single regimen and those of untreated patients. QFT-GIT from Cellestis Limited, Carnegie, Australia.

  • Table 2—

    Risk factors associated with QuantiFERON® in-tube (QFT-GIT) and tuberculin skin test (TST) positivity in subjects with rheumatic diseases: multivariate analysis

    QFT-GIT positiveTST positive
    OR (95% CI)p-valueOR (95% CI)p-value
    Male2.1 (1.1–4.2)0.011.65 (0.9–2.9)0.08
    BCG vaccinatedNANA3.8 (1.0–13.9)0.04
    Age yrs
     ≤29RefRef
     30–492.8 (0.3–23.4)0.38.6 (1.0–69.7)0.04
     50–696.8 (0.8–53.0)0.0614.7 (1.8–117.2)0.01
     >7015.9 (1.9–132.0)0.0113.2 (1.5–112.7)0.01
    Chest radiograph patterns
     No lesions of past TBRefRef
     Lesions of past TB1.3 (0.5–3.2)0.53.0 (1.3–6.8)0.005
     Other patterns0.4 (0.1–1.2)0.11.6 (0.7–3.4)0.1
    Immunosuppressive therapy including
     Steroids0.4 (0.2–0.9)0.030.3 (0.2–0.6)0.002
     DMARD1.1 (0.5–2.3)0.71.7 (0.9–3.4)0.09
     TNF-α inhibitors0.9 (0.4–2)0.80.3 (0.1–0.6)0.004
    Close contacts of patients with sputum-positive TB5.3 (1–28)0.046.5 (1.1–36.9)0.03
    Birth/residence in countries at high prevalence of TB1.1 (0.2–5.8)0.83.7 (1.1–12.3)0.03
    • OR: odds ratio; CI: confidence interval; BCG: bacillus Calmette–Guérin; TB: tuberculosis; DMARD: disease-modifying antirheumatic drugs; TNF-α: tumour necrosis factor-α; NA: not available; Ref: reference. QFT-GIT from Cellestis Limited, Carnegie, Australia.

  • Table 3—

    Association between number of risk factors for tuberculosis infection and QuantiFERON®-TB Gold in-tube (QFT-GIT) and tuberculin skin test (TST) positivity

    Number of risk factors#QFT-GIT positiveTST positivep-value¶
    OR (95% CI)p-valueOR (95% CI)p-value
    011
    13.30 (1.48–7.39)0.0042.57 (1.35–4.90)0.0040.730
    ≥25.71 (2.13–15.31)0.0015.35 (2.34–12.20)<0.001
    • OR: odds ratio; CI: confidence interval. #: aged ≥50 yrs, chest radiograph suggestive of a past tuberculosis (TB), close contact with patients with sputum-positive TB, birth/residence in a country with high incidence of TB; ¶: for the conjoint hypothesis of no difference in the estimates of the two models. QFT-GIT from Cellestis Limited, Carnegie, Australia.

  • Table 4—

    Estimate of the prevalence of latent tuberculosis using different approaches

    Test consideredEstimated rate % (95% CI)
    Only TST positive18.8 (14.9–22.7)
    Only QFT-GIT positive13.2 (9.8–16.5)
    QFT-GIT and TST positive9.9 (6.9–12.8)
    QFT-GIT among TST positive9.9 (6.9–12.8)
    At least one positive test22.1 (18–26.2)
    • CI: confidence interval; TST: tuberculin skin test; QFT-GIT: QuantiFERON®-TB Gold in-tube (Cellestis Limited, Carnegie, Australia).

  • Table 5—

    Concordance of the interferon-γ release assay (IGRA) and the tuberculin skin test (TST) for the screening of tuberculosis infection in the immunomediated inflammatory disease population

    StudyCountryIGRA kindSubjects nBCG %Indeterminate %κConcordant resultsDiscordant results
    TST+/IGRA+TST-/IGRA-TST-/IGRA+TST+/IGRA-
    Cobanoglu 21 TurkeyQFT-GIT68 cases38 controls10010.35.30.14-0.058 (13.1)023 (37.7)23 (63.8)1 (1.6)1 (2.8)29 (47.5)12 (33.3)
    Sellam# 22FranceELISPOT¶35 cases33 controls1000NANANANA
    Matulis+ 23SwitzerlandQFT-GIT1428360.1610 (7)60 (44.7)5 (3.5)34 (25.4)
    Pratt 24UKQFT-GIT10178.59.9NA§NA§NA§NA§
    Kobashi§ 25JapanQFT-G25260.312.60.2930 (13.6)120 (54.5)6 (2.8)64 (29.1)
    Dinser 26GermanyFlow cytometric assay975.100.316 (6.2)74 (76.3)10 (10.3)7 (7.2)
    Ponce de Leon 27PeruQFT-GIT101 cases93 controls80.280.61.900.370.5521 (20.8)16 (17.2)50 (49.5)61 (65.6)24 (23.8)5 (5.4)6 (5.9)11 (11.8)
    Vassiloupolos 28GreeceT-SPOT TB704000.3812 (17.1)39 (55.7)4 (5.7)15 (21.5)
    Bocchino 29ItalyQFT-GITT SPOT TB69692.82.82.85.80.570.4814 (20.9)12 (18.5)41 (61.2)39 (60)8 (11.9)9 (13.8)4 (6)5 (7.7)
    Greenber 30USAQFT-G61 cases42 controls27.823.311.52.4NANANANA
    Present dataItalyQFT-GIT3984.11.50.5539 (10)306 (77.8)13 (3.3)35 (8.9)
    • BCG: bacillus Calmette–Guérin; +: positive; -: negative; QFT-GIT: QuantiFERON®-TB Gold in-tube (culture filtrate protein (CFP)-10, early secreted antigenic target (ESAT)-6 and tuberculosis-7; Cellestis Limited, Carnegie, Australia); ELISPOT: enzyme-linked immunospot; QFT-G: QuantiFERON®-TB Gold (CFP-10 and ESAT-6, Carnegie); NA: not available. #: no direct comparison between the two tests. ¶: home-made ELISPOT with antigens CFP-10 and ESAT-6. +: TST analysed retrospectively. The median time between performing the TST and the QFT-GIT assay was 102 days (range 7–184). §: nonhomogeneous population including different underlying diseases (74 subjects had malignant diseases, 72 subjects were undergoing immunosuppressive treatment with steroids and/or tumour necrosis factor-α inhibitors, 52 subjects had diabetes mellitus, 50 subjects had chronic renal failure, four subjects had HIV infection). T-SPOT TB manufactured by Oxford Immunotec, Abingdon, UK.

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QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases
F. Bartalesi, S. Vicidomini, D. Goletti, C. Fiorelli, G. Fiori, D. Melchiorre, E. Tortoli, A. Mantella, M. Benucci, E. Girardi, M. M. Cerinic, A. Bartoloni
European Respiratory Journal Mar 2009, 33 (3) 586-593; DOI: 10.1183/09031936.00107608

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QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases
F. Bartalesi, S. Vicidomini, D. Goletti, C. Fiorelli, G. Fiori, D. Melchiorre, E. Tortoli, A. Mantella, M. Benucci, E. Girardi, M. M. Cerinic, A. Bartoloni
European Respiratory Journal Mar 2009, 33 (3) 586-593; DOI: 10.1183/09031936.00107608
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