Immune-mediated inflammatory diseases differently affect IGRAs' accuracy for latent tuberculosis infection diagnosis in clinical practice.

Irene Latorre,Juan Naves,Irma Casas,Carlos Ferrándiz,Jose Domínguez,Cristina Prat,Eugeni Domènech,Beatriz Muriel,Sonia Mínguez,Raquel Villar-Hernández,Esther García-García,José-Manuel Carrascosa,Lourdes Mateo

doi:10.1371/journal.pone.0189202

Abstract

BackgroundClinical accuracy of IGRAs remains unclear on patients with immune-mediated inflammatory diseases (IMIDs). Here, we assess the impact of immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB accuracy.MethodsPatients with IMIDs who required latent tuberculosis infection (LTBI) screening were enrolled and classified into: (i) 50 patients with inflammatory rheumatic diseases, (ii) 50 patients with psoriasis and (iii) 30 patients with Crohn’s disease. A total of 44 healthy individuals without immunosuppression were also included as controls. Tuberculin skin test (TST), T-SPOT.TB and QFN-G-IT assays were performed. IGRAs were performed following manufacturer’s instructions.ResultsImmunosuppressant’s intake was more frequent on patients with Crohn’s disease and psoriasis. Positive IGRAs and TST results were reduced in Crohn’s disease patients, whereas rate of indeterminate T-SPOT.TB results was increased in this group with respect to the other IMIDs analysed and controls. When IFN-γ response was studied, the levels of this cytokine after mitogen stimulation were significantly lower in Crohn’s and inflammatory rheumatic diseases than in psoriasis. Interestingly, psoriatic patients were the only ones not receiving corticosteroids. Furthermore, a negative correlation was observed between the IFN-γ secreted after mitogen stimulation and corticosteroids dose.ConclusionsIMIDs seem to negatively affect the clinical accuracy of IGRAs, being Crohn’s disease patients the most affected individuals due to their concomitant drug-profile and impaired immune response.

Highlights

Patients with immune-mediated inflammatory diseases (IMIDs) have a higher risk of tuberculosis (TB) reactivation than common population because of the intake of different immunosuppressive therapies and/or their main disease itself
Positive IGRAs and TST results were reduced in Crohn’s disease patients, whereas rate of indeterminate T-SPOT.TB results was increased in this group with respect to the other IMIDs analysed and controls
We have investigated the impact of different immunosuppressant therapies and IMIDs on QuantiFERON technology (QFN)-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB assays

Summary

Introduction

Patients with immune-mediated inflammatory diseases (IMIDs) have a higher risk of tuberculosis (TB) reactivation than common population because of the intake of different immunosuppressive therapies and/or their main disease itself. Tumour Necrosis Factor (TNF)-alpha (α) is a pro-inflammatory key cytokine playing an important role in the immune response against Mycobacterium tuberculosis It is crucial for maintaining the granuloma formation and containing the infection caused by the bacilli. There are two assay formats: QuantiFERON technology (QFN; Qiagen, Dusseldorf, Germany) and T-SPOT.TB (Oxford Immunotec, Abingdon, UK), both approved by the U.S Food and Drug Administration (FDA) and the CE (for their use in Europe). IGRAs’ methodology contain a positive control [stimulation with phytohaemagglutinin (PHA) as a mitogen] which detects the presence of anergy This control is very useful in individuals with a weak immune response due to the intake of several immunosuppressant therapies or the presence of a certain underlying disease. We assess the impact of immunosuppressants and IMIDs on QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB accuracy.

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Conclusion