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Interferon-gamma release assays in the detection of latent tuberculosis infection in patients with inflammatory arthritis scheduled for anti-tumour necrosis factor treatment

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Abstract

Biological agents, particularly anti-Tumour Necrosis Factor (TNF)-α agents, have emerged as an effective treatment in patients with chronic inflammatory diseases. An association between anti-TNF-α antibodies and reactivation of latent tuberculosis infection (LTBI) has been established. Appropriate screening for TB infection has become mandatory before starting a treatment based on TNF-α inhibition. The objective was to determine the usefulness of IFN-γ release assays in diagnosing LTBI in patients with inflammatory rheumatic diseases scheduled for anti-TNF-α treatment. The study included 53 individuals with inflammatory rheumatism. All patients had a TST, a chest radiograph, QuantiFERON Gold In-Tube (QFN-G-IT) and T-SPOT.TB. To investigate the influence of non-tuberculous mycobacteria (NTM) infections on non-BCG-vaccinated patients, with a positive TST result and both negative IFN-γ assays, we performed an ex vivo ELISPOT, stimulating the cells separately with NTM sensitins. TST was positive in 7 cases, T-SPOT.TB in 11 and QFN-G-IT in 9 cases. Agreement between TST and T-SPOT.TB and QFN-G-IT was 77.35% (κ = 0.33 and κ = 0.40, respectively), and between both in vitro tests, it was 83.01% (κ = 0.57). Of the three patients with positive TST and negative T-SPOT.TB and QFN-G-IT, one positive ELISPOT result was obtained after stimulation with NTM sensitins. Positive TST, T-SPOT.TB and QFN-G-IT results were not affected by the immunosuppressive therapies. IFN-γ release assays are useful methods for avoiding TST false-positive results, but in those patients with a high risk of developing active TB and in the absence of predictive value studies in this specific kind of population for knowing how safe is the use of IGRAs alone, the combined use of TST and IFN-γ tests should be recommended in order to increase the overall number of LTBI diagnoses.

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Acknowledgements

We warmly thank the patients for agreeing to participate in the study. The manuscript has been revised by a native English speaker who is both a professional translator and qualified philologist from The Language Advisory & Translation Unit of the Servei de Llengües at the Universitat Autònoma de Barcelona (Spain). J. Dominguez is a researcher funded by the “Miguel Servet” programme of the Instituto de Salud Carlos III (Spain).

Disclosures

None of the investigators have any financial interest in or a financial conflict with the subject matter or materials discussed in this manuscript. This work was supported by grants from the Sociedad Española de Neumología y Cirugía Torácica, Societat Catalana de Pneumologia (SOCAP), Fundació Catalana de Pneumologia (FUCAP) and Societat Catalana de Reumatologia (SCR). None of the scientific societies nor Inverness Medical Ibérica SAU (Barcelona, Spain), Cellestis (Carnegie, Australia) or Oxford Immunotec (Abingdon, UK) had a role in the study design, implementation, data collection, management, analysis, interpretation of the data, preparation, review or approval of the manuscript.

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Authors and Affiliations

  1. Servei de Reumatologia, Hospital Universitari Germans Trias i Pujol, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Carretera del Canyet s/n., 08916, Badalona, Spain

    Sonia Mínguez, Lourdes Mateo & Alejandro Olivé

  2. Servei de Microbiologia, Hospital Universitari Germans Trias i Pujol, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, CIBER Enfermedades Respiratorias. Institut de Salud Carlos III, Carretera del Canyet s/n., 08916, Badalona, Spain

    Irene Latorre, Alicia Lacoma, Jéssica Diaz & Jose Domínguez

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  1. Sonia Mínguez
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  2. Irene Latorre
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  3. Lourdes Mateo
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Correspondence to Jose Domínguez.

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Mínguez, S., Latorre, I., Mateo, L. et al. Interferon-gamma release assays in the detection of latent tuberculosis infection in patients with inflammatory arthritis scheduled for anti-tumour necrosis factor treatment. Clin Rheumatol 31, 785–794 (2012). https://doi.org/10.1007/s10067-012-1938-z

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