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Comparison of in vitro-specific blood tests with tuberculin skin test for diagnosis of latent tuberculosis before anti-TNF therapy
  1. Jérémie Sellam1,*,
  2. Haifa Hamdi2,*,
  3. Carine Roy3,
  4. Gabriel Baron3,
  5. Marc Lemann4,
  6. Xavier Puéchal5,
  7. Maxime Breban6,
  8. Francis Berenbaum7,
  9. Marc Humbert8,
  10. Karin Weldingh9,
  11. Dominique Salmon10,
  12. Philippe Ravaud3,
  13. Dominique Emilie2,
  14. Xavier Mariette1
  1. 1
    Rhumatologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Le Kremlin Bicêtre, France
  2. 2
    INSERM UMR-S764, Service de Microbiologie-Immunologie Biologique, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Institut Paris-Sud sur les Cytokines, Université Paris-Sud, Clamart, France
  3. 3
    Département d’Epidémiologie, Biostatistique et Recherche Clinique, Groupe Hospitalier Bichat Claude-Bernard, Assistance Publique-Hôpitaux de Paris, Université Paris VII, Paris, France
  4. 4
    Service de Gastro-entérologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France
  5. 5
    Service de Rhumatologie, Centre hospitalier du Mans, Le Mans, France
  6. 6
    Service de Rhumatologie, Hôpital Ambroise Paré, Assistance Publique-Hôpitaux de Paris, Boulogne, France
  7. 7
    Service de Rhumatologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Paris, France
  8. 8
    Service de Pneumologie, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris-Sud, Clamart, France
  9. 9
    Department of Infectious Disease and Immunology, Statens Serum Institut, Copenhagen, Denmark
  10. 10
    Service de Médecine interne et maladies infectieuses, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France
  1. Pr Xavier Mariette, Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France; xavier.mariette{at}bct.ap-hop-paris.fr

Abstract

Introduction: Latent tuberculosis infection (LTBI) is detected with the tuberculin skin test (TST) before anti-TNF therapy. We aimed to investigate in vitro blood assays with TB-specific antigens (CFP-10, ESAT-6), in immune-mediated inflammatory diseases (IMID) for LTBI screening.

Patients and methods: Sixty-eight IMID patients with (n = 35) or without (n = 33) LTBI according to clinico-radiographic findings or TST results (10 mm cutoff value) underwent cell proliferation assessed by thymidine incorporation and PKH-26 dilution assays, and IFNγ-release enzyme-linked immunosorbent spot (ELISPOT) assays with TB-specific antigens.

Results: In vitro blood assays gave higher positive results in patients with LTBI than without (p<0.05), with some variations between tests. Among the 13 patients with LTBI diagnosed independently of TST results, 5 had a negative TST (38.5%) and only 2 a negative blood assays result (15.4%). The 5 LTBI patients with negative TST results all had positive blood assays results. Ten patients without LTBI but with intermediate TST results (6–10 mm) had no different result than patients with TST result ⩽5 mm (p>0.3) and lower results than those with LTBI (p<0.05) on CFP-10+ESAT-6 ELISPOT and CFP-10 proliferation assays.

Conclusion: Anti-TB blood assays are beneficial for LTBI diagnosis in IMID. Compared with TST, they show a better sensitivity, as seen by positive results in 5 patients with certain LTBI and negative TST, and better specificity, as seen by negative results in most patients with intermediate TST as the only criteria of LTBI. In the absence of clinico-radiographic findings for LTBI, blood assays could replace TST for antibiotherapy decision before anti-TNF.

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Footnotes

  • These authors have contributed equally to the study.

  • This work was promoted by the Club Rhumatismes et Inflammation with a grant of Schering Plough France.

  • Competing interests: None.

  • Abbreviations:
    BCG
    bacille Calmette–Guérin
    CFP-10
    culture fibrate protein-10
    ELISPOT
    enzyme-linked immunosorbent spot
    ESAT-6
    early secretory antigen target-6
    IFNγ
    interferon gamma
    IMID
    immune-mediated inflammatory diseases
    LTBI
    Latent tuberculosis infection
    TB
    tuberculosis
    TST
    tuberculin skin test