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肿瘤坏死因子拮抗剂治疗银屑病患者的结核干扰素 -γ释放试验:体内和体外分析。

Interferon-γ release assay for tuberculosis in patients with psoriasis treated with tumour necrosis factor antagonists: in vivo and in vitro analysis.

机构信息

Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.

出版信息

Br J Dermatol. 2013 Nov;169(5):1133-40. doi: 10.1111/bjd.12544.

Abstract

BACKGROUND

Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers.

OBJECTIVES

To investigate the longitudinal changes of interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens by serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing in patients with psoriasis during long-term anti-TNF therapy. The direct in vitro effect of adalimumab on IFN-γ secretion was also evaluated.

METHODS

In total, 148 patients with psoriasis designated to start anti-TNF treatment were enrolled. We performed a tuberculin skin test at screening, and QFT-GIT at baseline and serially for 24 months after TNF antagonist onset.

RESULTS

At screening, QFT-GIT was positive in 22.3% of the patients, negative in 73.6% and indeterminate in 4%. The IFN-γ response following isoniazid therapy declined and became QFT-GIT negative in 8% of 26 patients with LTBI; in 69% of subjects with LTBI the QFT-GIT remained persistently positive with a significant increase of IFN-γ levels during the follow-up, even if no cases of active tuberculosis were found. Variations of IFN-γ levels were observed also in 7% of 27 patients without LTBI who switched to positive QFT-GIT after 12 or 18 months of biologic therapy, suggesting a new occurrence or reactivation of LTBI. In vitro data showed that in the presence of adalimumab the IFN-γ levels were significantly reduced in a dose-dependent manner (P < 0.05).

CONCLUSIONS

Fluctuations of IFN-γ release may occur in patients with psoriasis treated with TNF antagonists. The clinical use of repeated blood tests and the correct interpretation of individual IFN-γ changes could be useful in identifying possible cases of LTBI reactivation or newly acquired tuberculosis infection during long-term anti-TNF treatment.

摘要

背景

在开始使用肿瘤坏死因子(TNF)阻滞剂之前,银屑病患者必须进行潜伏性结核感染(LTBI)筛查。

目的

通过对银屑病患者在长期抗 TNF 治疗期间进行系列结核分枝杆菌特异性抗原酶联免疫斑点法(QuantiFERON-TB Gold In-Tube,QFT-GIT)检测,探讨干扰素(IFN)-γ反应的纵向变化。还评估了阿达木单抗对 IFN-γ分泌的直接体外作用。

方法

共纳入 148 例拟开始抗 TNF 治疗的银屑病患者。我们在筛查时进行结核菌素皮肤试验,在基线时和 TNF 拮抗剂开始后 24 个月时进行 QFT-GIT 检测。

结果

在筛查时,22.3%的患者 QFT-GIT 阳性,73.6%的患者 QFT-GIT 阴性,4%的患者 QFT-GIT 不确定。26 例 LTBI 患者中,8%的患者在异烟肼治疗后 IFN-γ反应下降并转为 QFT-GIT 阴性;69%的 LTBI 患者 QFT-GIT 持续阳性,且在随访期间 IFN-γ水平显著升高,尽管未发现活动性结核病。在没有 LTBI 的 27 例患者中,也观察到 7%的患者在接受生物治疗 12 或 18 个月后转为 QFT-GIT 阳性,提示 LTBI 的新发生或再激活。体外数据显示,在阿达木单抗存在的情况下,IFN-γ水平呈剂量依赖性显著降低(P<0.05)。

结论

接受 TNF 拮抗剂治疗的银屑病患者 IFN-γ释放可能出现波动。重复进行血液检测并正确解释个体 IFN-γ变化,有助于在长期抗 TNF 治疗期间识别 LTBI 再激活或新获得的结核感染的可能病例。

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