Role of the T-cell interferon-gamma release assays in preventing reactivation of latent tuberculosis infection in immunosuppressed patients in treatment with anti-TNF agents

Abstract

Chronic inflammatory diseases such as Crohn's disease or ulcerative colitis, are major autoimmune disorders with increasing incidence.1 Although conventional therapies based on corticosteroids and immunosuppressants play a major role in the management of these diseases, the corticoisteroid-associated adverse events and the existence of immunosuppressant-refractory patients have prompted the development of new disease-modifying therapies. Biological agents, especially the anti-Tumor Necrosis Factor (TNF)-α agents, have emerged as an effective treatment for these diseases.1 One of the primary concerns with anti-TNF-α agents is the possibility of collateral effects on host defence mechanisms. Patients undergoing TNF-α inhibition are at increased risk of developing severe infections. A temporal association between anti-TNF-α antibodies and reactivation of latent tuberculosis (TB) infection has been established.2,3 In fact, TNF-α is one of the key molecules involved in granuloma formation and maintenance. Therefore, previous to start TNF-α inhibition, appropriate screening of latent TB infection and early active TB diagnosis has become mandatory.4 The current guidelines for screening latent TB are based on the tuberculin skin test (TST) that has been used since the late 1800s for diagnosing latent TB infection. TST attempts to measure cell-mediated immunity as assessed by a delayed-type hypersensitivity response to its components.5,6 TST is produced by steaming cultures of Mycobacterium tuberculosis in a sterilizer and purifying the proteins (purified protein derivative [PPD]) by repeated precipitation with neutral ammonium sulphate.7 In the TST, 0.1 ml of PPD solution are injected intradermically in the forearm of the patient. After 48 h, the diameter of induration is measured. A TST induration > 5mm is considered positive, independently of the Mycobacterium bovis bacilli Calmette-Guerin (BCG) vaccination status. In case of induration < 5mm, it is necessary to repeat the TST between 1–2 weeks later (booster effect), also considering as positive …