Diagnosis of tuberculosis infection by interferon-gamma release assays in patients with psoriasis
Introduction
Biological therapies such as anti-tumour necrosis factor (TNF)-α antagonists have emerged as effective treatment options for chronic inflammatory diseases like psoriasis.1 However, the use of these therapies is clearly associated with risk of tuberculosis (TB) development and latent tuberculosis infection (LTBI) reactivation.2 TNF-α is a key pro-inflammatory cytokine involved in the immune response against Mycobacterium tuberculosis (MTB). It is essential for maintaining tuberculous granuloma and thus containing the infection. As a consequence, it is mandatory to rule out LTBI and active TB prior anti-TNF-α medical prescription as well as during the monitoring of therapy.3
Tuberculin skin test (TST) has been used for the last 100 years as a classical method for diagnosing LTBI. However, it has a reduced specificity due to cross-reactivity with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine strain and non-tuberculous mycobacteria (NTM). Furthermore, it has a low sensitivity in high-risk individuals with an impaired cellular immunity such as those with inflammatory diseases under immunosuppressive agents.
A decade ago, interferon-γ release assays (IGRAs) were developed as an aid for diagnosing LTBI. IGRAs are based on in vitro interferon (IFN)-γ detection released by sensitised T cells after specific MTB antigens stimulation (ESAT-6, CFP-10 and TB7.7). Currently, there are two U.S. Food and Drug Administration commercially available formats: QuantiFERON-TB Gold In-Tube (QFN-G-IT, QIAGEN, Düsseldorf, Germany) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK). Both assays are reported to avoid false-positive results in BCG vaccinated patients and most of NTM infections. In addition, they correlate better than TST with exposure to MTB.4, 5, 6
There is also growing evidence corroborating that T-cell based assays are useful tools for diagnosing LTBI in patients with a deficient cellular immune response,7, 8 such as children,9 patients with human immunodeficiency virus (HIV)10 and patients receiving immunosuppressive therapies.11, 12 Several studies have assessed their utility for LTBI diagnosis in patients with chronic inflammatory diseases including psoriasis.13 However, in some cases, evaluated populations are highly diverse resulting in a mixture of different inflammatory diseases analysed, immunosuppressive regimens and QFN versions. Considering the importance of ruling out LTBI in this kind of population, there is an urgent need to accurately evaluate IGRAs in this context. In our study, we performed a direct comparison between both T-cell based assays (QFN-G-IT and T-SPOT.TB) and TST in patients with moderate-to-severe psoriasis taking different immunosuppressant drug-regimens. Although there is some data available in this direction, investigations are still limited and should be further investigated.
Section snippets
Study setting and patient recruitment
We prospectively recruited 103 patients with moderate-to-severe psoriasis who attended Dermatology Unit of Hospital Universitari Germans Trias i Pujol (Badalona, Spain) between November 2010 and April 2012 for LTBI screening. A detailed questionnaire was recorded in order to indicate: gender, age, place of birth, immigration status, results of any previous TST, TST induration, details of any contact with an active TB patient, history of previous active TB, chest radiograph and immunosuppression
Diagnostic test performance
The overall number of positive results in all patients studied was 17/103 (16.5%), 18/103 (17.5%) and 9/103 (8.7%) using T-SPOT.TB, QFN-G-IT and TST, respectively. Differences in the percentage of positive results between TST with T-SPOT.TB and QFN-G-IT were significant (p = 0.005 and p = 0.008, respectively). In contrast, differences were not statistically significant when comparing both IGRAs (p = 0.448). Twenty-five of the 103 subjects (24.3%) enrolled were positive for at least one of the
Discussion
In the present study we have investigated the potential clinical performance of T-SPOT.TB and QFN-G-IT for LTBI diagnosis in patients with psoriasis under different immunosuppressive drug-regimens. We found that IGRAs were positive in a significantly higher percentage of cases compared to TST. Moreover, in a considerable percentage of patients with a negative TST (17%) at least one of the IGRAs was positive, suggesting that in vitro assays are less influenced by immune deregulation. Many
Conflict of interest
I. Latorre, J. Díaz, C. Prat and J. Domínguez are members of the European Tuberculosis Network (TB-NET) Group. J. Domínguez is a researcher founded from the Miguel Servet programme of the Instituto de Salud Carlos III (Spain). None of the researchers have any financial interest or financial conflict with the subject matter or materials discussed in the manuscript. None of the scientific societies, and neither QIAGEN (Düsseldorf, Germany) or Oxford Immunotec (Abingdon, UK) had a role in the
Acknowledgements
We thank the nursing staff of dermatology department Anna Julià and Mercè Ferrer for technical assistance.
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2018, Biosensors and BioelectronicsCitation Excerpt :Individuals with deficiency in either IFN-γ production, receptor expression or the signaling pathway (IL-2/IL-23/IFN-γ) show high incidence of infections due to Salmonella or intracellular bacteria as Mycobacterium (Lamhamedi et al., 1998; Noordzij et al., 2007) and viruses (Dammermann et al., 2015). On the contrary, the increased production of IFN-γ is associated to an improved anti-tumor response (Dunn et al., 2006), and plays also an important role in autoimmune disorders (Baccala et al., 2005; Pollard et al., 2013), for instance in Systemic Lupus Erythematosus (Welcher et al., 2015) and psoriasis (Latorre et al., 2014), among others. Interferon-γ release assay (IGRA) is based on the production and quantification of IFN-γ upon in vitro stimulation of the T lymphocytes with specific antigens.
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2017, Journal of InfectionCitation Excerpt :The proportion of indeterminate results obtained by IGRAs varies between studies and study population. Some studies describe a higher number of indeterminate results obtained by QFN-G-IT than T-SPOT.TB,40,42,48 whereas others describe the opposite.43,53 Our study agrees with the latter as from the seven indeterminate results obtained, five were obtained by T-SPOT.TB, one by QFN-G-IT and two by IP-10 detection.
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- d
Current address: ICREA Infection Biology Laboratory, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
- e
These authors contributed equally to this work.