IL-6、TNF-α、GR-α、GR-βmRNA与常见眼眶疾病患者对糖皮质激素敏感性的关系

Application of the mRNA of IL-6,TNF-α,GR-α and GR-β in evaluating the glucocorticoids sensitivity of patients with common orbital diseases

目的分析白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、糖皮质激素受体(glucocorticoid receptor,GR)α亚型(GR)及β亚型(GR-β)mRNA与常见眼眶疾病如甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)和特发性眼眶炎性假瘤患者(idiopathic orbital inflammatory pseudotumor,IOIP)与糖皮质激素(glucocorticoid,GC)敏感性的关系。方法收集首都医科大学附属北京同仁医院眼肿瘤门诊TAO患者62例及IOIP患者36例,包括糖皮质激素敏感组和抵抗组。收集EDTA-K 2外周抗凝血,将标本一分为二,分为处理组和对照组。处理组加入终浓度为100 nmol/L的地塞米松,对照组加入等体积的二甲基亚砜,室温下处理7 h。实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction,q-PCR)法检测患者外周血白细胞GR-α、GR-β、IL-6及TNF-α的mRNA表达量,分析其与患者对GC敏感性的关系。受试者工作特征(receiver operating characteristic,ROC)曲线评价GR-α/β指标区分患者对GC敏感性的效能。结果TAO敏感组和抵抗组IL-6、TNF-α、GR-α及β的差异无统计学意义(P>0.05);GR-α/β的差异有统计学意义(P<0.05);GR-α/β的ROC曲线下面积(area under the ROC curve,AUC)为0.70(95%CI:0.54~0.87),临界值取1.255,此时灵敏度和特异度分别为85%和53%。IOIP敏感组与抵抗组IL-6、TNF-α及GR-α的差异无统计学意义(P>0.05);GR-β及GR-α/β在两组之间差异有统计学意义(P<0.05);GR-α/β的AUC为0.77(95%CI:0.58~0.95),临界值取1.005,此时灵敏度和特异度分别为90%和72%。结论GR-α/β有望成为预测TAO和IOIP患者对GC敏感性的指标。

Objective To analyze the glucocorticoids(GC)sensitivity of patients with thyroid-associated ophthalmopathy(TAO)and idiopathic orbital inflammatory pseudotumor(IOIP)based on laboratory indicators of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),glucocorticoid receptor(GR)-α and GR-β.Methods A total of 62 TAO patients and 36 IOIP patients from the Eye Tumor Clinic of Beijing Tongren Hospital,Capital Medical University were enrolled and divided into glucocorticoid sensitive and resistant groups(GCR group).The EDTA-K2 peripheral anticoagulant blood of the patients was collected,and it was divided into treatment group and control group.The blood sample in the treatment group was treated with dexamethasone at final concentration of 100 nmol/L at room temperature for 7h,while the control group was treated with an equal volume of dimethy1 sulfoxide.The real-time fluorescent quantitative PCR(q-PCR)was applied to detect the mRNA of IL-6,TNF-α,GR-αand GR-βsubtype from patient’s peripheral blood leukocyte to analyze and evaluate the sensitivity of patients to GC.The diagnostic efficacy of the detection indicators was analyzed by receiver operating characteristic(ROC)curve,and the area under the ROC curve(AUC)was compared with each other.Results Comparison of the sensitive group with the GCR group in TAO patients indicated that the differences of IL-6,TNF-α,GR-α and β were not statistically significant(P>0.05),the AUC of the ratio of GR-α/β in TAO patients was 0.70(95%CI:0.54-0.87)and the critical value was 1.255.Comparison of the sensitive group with the GCR group in IOIP patients indicated that there was no significant difference in IL-6,TNF-α,and GR-α,but statistical significant differences in GR-β and GR-α/β(P<0.05),the AUC of the ratio of GR-α/β in IOIP patients was 0.77(95%CI:0.58-0.95)and the critical value was 1.005.Conclusion GR-α/βcould be an indicator for predicting the sensitivity of TAO and IOIP patients to GC.