利妥昔单抗治疗对不同结核分枝杆菌感染状态的类风湿关节炎患者 Quantiferon 检测中释放的干扰素-γ水平的影响。

The effects of rituximab therapy on released interferon-γ levels in the QuantiFERON assay among RA patients with different status of Mycobacterium tuberculosis infection.

机构信息

Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan.

出版信息

Rheumatology (Oxford). 2013 Apr;52(4):697-704. doi: 10.1093/rheumatology/kes365. Epub 2012 Dec 22.

DOI:10.1093/rheumatology/kes365

PMID:23264552

Abstract

OBJECTIVE

To investigate the influence of rituximab therapy on released IFN-γ levels in the QuantiFERON-TB-Gold In-Tube (QFT-GIT) assay among RA patients of different Mycobacterium tuberculosis infection status.

METHODS

Change in levels of released IFN-γ in the QFT-GIT assay was evaluated in RA patients who had received 1 year of rituximab treatment. A tuberculin skin test was performed using the Mantoux method and the QFT-GIT assay was performed by measuring IFN-γ levels in whole blood treated with tuberculosis (TB)-specific antigens.

RESULTS

Among 56 patients, 43 patients were presumed to be without latent TB infection (LTBI), 7 patients had LTBI and 6 patients had anti-TNF-associated TB. During the 1-year period of rituximab therapy, no patient developed active TB or had QFT-GIT conversion. No significant change in released IFN-γ levels on QFT-GIT assay after 1-year rituximab therapy was observed in patients with LTBI [3.39 (1.21) vs 2.47 (0.82) IU/ml] or in those with anti-TNF-associated TB [1.06 (0.22) vs 0.87 (0.39) IU/ml]. Rituximab did not inhibit TB antigen-stimulated IFN-γ production ex vivo. The frequency of circulating CD19(+) B cells was significantly decreased [8.56 (0.84) vs 1.52 (0.44)%, P < 0.001], paralleling the decrease in RF titre [318.5 (76.0) vs 115.1 (32.1) IU/ml, P < 0.001] and DAS28 [6.49 (0.13) vs 4.59 (0.14), P < 0.001] after 1 year of rituximab therapy. However, there was no significant change in the frequency of CD3(+) T cells after rituximab therapy.

CONCLUSION

No occurrence of active TB or QFT-GIT conversion was observed in patients receiving 1 year of rituximab therapy. No significant effect of rituximab therapy on IFN-γ release levels was observed in patients with LTBI and with anti-TNF-α-associated TB. Rituximab may be an alternative therapeutic agent for these patients.

摘要

目的

研究利妥昔单抗治疗对不同结核分枝杆菌感染状态类风湿关节炎（RA）患者的 QuantiFERON-TB-Gold In-Tube（QFT-GIT）检测中释放 IFN-γ水平的影响。

方法

对接受利妥昔单抗治疗 1 年的 RA 患者评估 QFT-GIT 检测中释放 IFN-γ水平的变化。采用结核菌素皮肤试验（Mantoux 法）和 QFT-GIT 检测，通过测量结核（TB）特异性抗原处理的全血中 IFN-γ 水平。

结果

在 56 例患者中，43 例患者被认为无潜伏性结核感染（LTBI），7 例患者有 LTBI，6 例患者有抗 TNF-α相关的 TB。在利妥昔单抗治疗的 1 年期间，无患者发生活动性 TB 或 QFT-GIT 转换。LTBI [3.39（1.21）比 2.47（0.82）IU/ml]或抗 TNF-α相关 TB [1.06（0.22）比 0.87（0.39）IU/ml]患者在 1 年利妥昔单抗治疗后 QFT-GIT 检测中释放 IFN-γ水平无显著变化。利妥昔单抗未抑制 TB 抗原刺激的 IFN-γ产生。循环 CD19(+)B 细胞的频率显著降低[8.56（0.84）比 1.52（0.44）%，P<0.001]，与 RF 滴度[318.5（76.0）比 115.1（32.1）IU/ml，P<0.001]和 DAS28[6.49（0.13）比 4.59（0.14），P<0.001]在利妥昔单抗治疗 1 年后下降相一致。然而，利妥昔单抗治疗后 CD3(+)T 细胞的频率无显著变化。