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γ干扰素释放试验在肿瘤坏死因子治疗的炎症性关节炎患者潜伏性结核感染检测中的应用。

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

机构信息

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

出版信息

Clin Rheumatol. 2012 May;31(5):785-94. doi: 10.1007/s10067-012-1938-z. Epub 2012 Jan 21.

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.

摘要

生物制剂,特别是抗肿瘤坏死因子(TNF)-α 制剂,已成为治疗慢性炎症性疾病患者的有效方法。已经证实抗 TNF-α 抗体与潜伏性结核感染(LTBI)的再激活之间存在关联。在开始基于 TNF-α 抑制的治疗之前,进行适当的 TB 感染筛查已成为强制性要求。本研究旨在确定 IFN-γ 释放试验在诊断计划接受抗 TNF-α 治疗的炎症性风湿病患者 LTBI 中的有用性。该研究纳入了 53 名炎症性风湿病患者。所有患者均进行了 TST、胸部 X 线检查、QuantiFERON Gold In-Tube(QFN-G-IT)和 T-SPOT.TB。为了研究非结核分枝杆菌(NTM)感染对未接种 BCG 的 TST 阳性且两种 IFN-γ 检测均为阴性的患者的影响,我们进行了体外 ELISPOT 检测,分别用 NTM 致敏原刺激细胞。TST 阳性 7 例,T-SPOT.TB 阳性 11 例,QFN-G-IT 阳性 9 例。TST 与 T-SPOT.TB 和 QFN-G-IT 的一致性分别为 77.35%(κ=0.33 和 κ=0.40),两种体外检测之间的一致性为 83.01%(κ=0.57)。在 TST 阳性、T-SPOT.TB 和 QFN-G-IT 阴性的 3 名患者中,1 名患者在用 NTM 致敏原刺激后获得了阳性 ELISPOT 结果。阳性 TST、T-SPOT.TB 和 QFN-G-IT 结果不受免疫抑制治疗的影响。IFN-γ 释放试验是避免 TST 假阳性结果的有用方法,但在那些发生活动性 TB 风险较高的患者中,以及在针对这一特定人群进行预测价值研究之前,尚不清楚单独使用 IGRAs 的安全性如何,因此应推荐联合使用 TST 和 IFN-γ 检测,以增加 LTBI 诊断的总体数量。

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