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T-Cell Profiling and the Immunodiagnosis of Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease

Arias-Guillén, Miguel MD*; Riestra, Sabino MD, PhD; de Francisco, Ruth MD; Palacios, Juan José MD, PhD; Belda, José MD, PhD§; Escalante, Patricio MD, MSc; Pérez-Martínez, Isabel MD; Molinos, Luis M. PhD; Garcia-Clemente, Marta MD, PhD*; Pando-Sandoval, Ana MD*; Rodrigo, Luis MD, PhD; Prieto, Amador MD; Martínez-Camblor, Pablo PhD**; Losada, Ana RN*; Casan, Pere MD, PhD*

doi: 10.1097/01.MIB.0000438429.38423.62
Original Basic Science Articles

Background: Factors associated with performance of interferon-γ release assays (IGRA) and the tuberculin skin test (TST) in screening for latent tuberculosis infection in patients with inflammatory bowel diseases (IBD) are still poorly understood. The influence of peripheral T-cell subset counts on the results also remain unclear.

Methods: Prospective single-center study in 205 patients with IBD. Latent tuberculosis infection screening included a chest radiograph, TST (retest if negative), and 2 IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT) and TSPOT-TB (TSPOT). T-cell subpopulations were determined by flow cytometry.

Results: Twenty-one (10.2%) patients had an abnormal chest radiograph, 55 (26.8%) had a positive TST, 16 (7.8%) had a positive QFT-GIT, and 25 (12.6%) had a positive TSPOT. TST positivity was lower in patients on ≥2 immunosuppressants compared with the controls (5-aminosalicylic acid treatment) (10.4% versus 38.2%, respectively) (P = 0.0057). No other drugs influenced TST or IGRA positivity. In patients on corticosteroid treatment, anti-TNF treatment, or ≥2 immunosuppressants, IGRAs detected 10 cases of latent tuberculosis infection not identified by TST. TSPOT and QFT-GIT increased yield by 56% and 22%, respectively. No significant differences in T-cell subpopulations were found between patients with positive or negative TST or TSPOT results. However, patients with positive QFT-GIT findings had more CD8+ T cells (mean, 883 ± 576 versus 484 ± 385 cells per microliter in patients with negative results) (P = 0.022).

Conclusions: IGRAs can improve TST-based screening in patients with IBD on immunosuppressive therapy. A low CD8+ count can affect QFT-GIT results. We suggest combining TSPOT and TST screening in patients with IBD on immunosuppressants.

Article first published online 27 December 2013

*Department of Respiratory Medicine, Instituto Nacional de Silicosis, Hospital Universitario Central de Asturias, Oviedo, Spain;

Department of Digestive Diseases, Hospital Universitario Central de Asturias, Oviedo, Spain;

Department of Microbiology, Mycobacterial Reference Unit, Hospital Universitario Central de Asturias, Oviedo, Spain;

§Department of Respiratory Medicine, Hospital Arnau de Villanova, Valencia, Spain;

Division of Pulmonary and Critical Care Medicine and Mayo Clinic Center for Tuberculosis, Mayo Clinic, Rochester, Minnesota;

Department of Radiology, Hospital Universitario Central de Asturias, Oviedo; and

**Oficina de Investigación Biosanitaria, Hospital Universitario Central de Asturias, Oviedo, Spain.

Reprints: Miguel Arias-Guillén, MD, Department of Respiratory Medicine, Instituto Nacional de Silicosis, Hospital Universitario Central de Asturias, C/ Doctor Bellmunt, Oviedo 33006, Spain (e-mail: miguelariasguillen@gmail.com).

Dr. Arias-Guillén has no conflicts of interest to disclose: his work was funded by the Society of Respiratory Tract Diseases of Asturias (Sociedad Asturiana de Patología del Aparato Respiratorio). Dr. Riestra has worked as a consultant for the following companies: MSD, Abbott, Shire Sabino; he has provided expert testimony for Shire and received support for attending meetings from Abbott and MSD. Dr. de Francisco has received funding to attend meetings from Abbott and MSD. Dr. Palacios has received funding to attend meetings from Werfen Group and ALERE Healthcare. The other authors have no conflicts of interest to disclose.

Received September 19, 2013

Accepted November 9, 2013

© Crohn's & Colitis Foundation of America, Inc.
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