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自身免疫性疾病免疫抑制患者中潜伏性结核的检测:结核分枝杆菌抗原特异性干扰素γ检测的性能

Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon gamma assay.

作者信息

Matulis G, Jüni P, Villiger P M, Gadola S D

机构信息

Department of Rheumatology and Clinical Immunology/Allergology, University of Bern, Switzerland.

出版信息

Ann Rheum Dis. 2008 Jan;67(1):84-90. doi: 10.1136/ard.2007.070789. Epub 2007 Jul 20.

Abstract

OBJECTIVE

To analyse the performance of a new M. tuberculosis-specific interferon gamma (IFNgamma) assay in patients with chronic inflammatory diseases who receive immunosuppressive drugs, including tumour necrosis factor alpha (TNFalpha) inhibitors.

METHODS

Cellular immune responses to the M. tuberculosis-specific antigens ESAT-6, CFP-10, TB7.7 were prospectively studied in 142 consecutive patients treated for inflammatory rheumatic conditions. Results were compared with tuberculin skin tests (TSTs). Association of both tests with risk factors for latent M. tuberculosis infection (LTBI) and BCG vaccination were determined and the influence of TNFalpha inhibitors, corticosteroids, and disease modifying antirheumatic drugs (DMARDs) on antigen-specific and mitogen-induced IFNgamma secretion was analysed.

RESULTS

126/142 (89%) patients received immunosuppressive therapy. The IFNgamma assay was more closely associated with the presence of risk factors (odds ratio (OR) = 23.8 (95% CI 5.14 to 110) vs OR = 2.77 (1.22 to 6.27), respectively; p = 0.009), but less associated with BCG vaccination than the TST (OR = 0.47 (95% CI 0.15 to 1.47) vs OR = 2.44 (0.74 to (8.01), respectively; p = 0.025). Agreement between the IFNgamma assay and TST results was low (kappa = 0.17; 95% CI 0.02 to 0.32). The odds for a positive IFNgamma assay strongly increased with increasing prognostic relevance of LTBI risk factors. Neither corticosteroids nor conventional DMARDs significantly affected IFNgamma responses, but the odds for a positive IFNgamma assay were decreased in patients treated with TNFalpha inhibitors (OR = 0.21 (95% CI 0.07 to 0.63), respectively; p = 0.006).

CONCLUSIONS

These results demonstrate that the performance of the M. tuberculosis antigen-specific IFNgamma ELISA is better than the classic TST for detection of LTBI in patients receiving immunosuppressive therapy for treatment of systemic autoimmune disorders.

摘要

目的

分析一种新型结核分枝杆菌特异性干扰素γ(IFNγ)检测方法在接受免疫抑制药物(包括肿瘤坏死因子α(TNFα)抑制剂)治疗的慢性炎症性疾病患者中的表现。

方法

前瞻性研究了142例连续接受炎性风湿性疾病治疗的患者对结核分枝杆菌特异性抗原ESAT-6、CFP-10、TB7.7的细胞免疫反应。将结果与结核菌素皮肤试验(TST)进行比较。确定了两种检测方法与潜伏性结核分枝杆菌感染(LTBI)风险因素及卡介苗接种的相关性,并分析了TNFα抑制剂、皮质类固醇和改善病情抗风湿药物(DMARDs)对抗原特异性和丝裂原诱导的IFNγ分泌的影响。

结果

142例患者中有126例(89%)接受了免疫抑制治疗。IFNγ检测与风险因素的存在更密切相关(优势比(OR)分别为23.8(95%CI 5.14至110)和OR = 2.77(1.22至6.27);p = 0.009),但与卡介苗接种的相关性低于TST(OR分别为0.47(95%CI 0.15至1.47)和OR = 2.44(0.74至8.01);p = 0.025)。IFNγ检测与TST结果之间的一致性较低(kappa = 0.17;95%CI 0.02至0.32)。IFNγ检测呈阳性的几率随着LTBI风险因素预后相关性的增加而显著增加。皮质类固醇和传统DMARDs均未显著影响IFNγ反应,但接受TNFα抑制剂治疗的患者中IFNγ检测呈阳性的几率降低(OR分别为0.21(95%CI 0.07至0.63);p = 0.006)。

结论

这些结果表明,在接受免疫抑制治疗以治疗全身性自身免疫性疾病的患者中,结核分枝杆菌抗原特异性IFNγ ELISA检测LTBI的性能优于经典TST。

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