The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy.

Yu Jung Jung,Dong Kyoung Jang,Kyeongman Jeon,Hye In Woo,Eun-Suk Kang,Eun Mi Koh,Won-Jung Koh,Hoon Suk Cha,Nam Yong Lee

doi:10.1371/journal.pone.0141033

Abstract

ObjectiveWe compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring.MethodsBefore starting TNF-α antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-α antagonist therapy.ResultsAt the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8% (k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-α antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection.ConclusionThis study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden.

Highlights

Reactivation of latent tuberculosis infection (LTBI) is one of the major complications of tumor necrosis factor (TNF)-α antagonist therapy in patients with rheumatic diseases [1, 2]
Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by TSPOT.TB, while QuantiFERON-TB Gold InTube (QFT-GIT) testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy
This study demonstrated the need to capitalize on sensitive Interferon-gamma release assays (IGRAs) to monitor for LTBI in atrisk patients for a more sensitive diagnosis in countries with an intermediate TB burden

Summary

Introduction

Reactivation of latent tuberculosis infection (LTBI) is one of the major complications of tumor necrosis factor (TNF)-α antagonist therapy in patients with rheumatic diseases [1, 2]. The chance of reactivation may increase with certain medical conditions such as human immunodeficiency virus (HIV) infection and concurrent medication including immunosuppressive drugs [3, 4], which are administered to most patients with rheumatic diseases. To avoid these possible side effects, testing should be performed prior to initiating TNF-α antagonist therapy. There have been extensive efforts to develop better tools for detection of LTBI in patients with rheumatic diseases who require immunosuppressive agents such as TNF-α antagonist. There is no consensus on currently available IGRA utilization for diagnosis of LTBI, because IGRA performance varies according to study group and design

Methods

Results

Conclusion