Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 1, 00185, Rome, Italy.
Br J Dermatol. 2013 Nov;169(5):1133-40. doi: 10.1111/bjd.12544.
Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers.
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.
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.
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).
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.
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。
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。
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。
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)。
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。