Division of Gastroenterology, Hospital for Children and Adolescents and Helsinki University Central Hospital, University of Helsinki, Helsinki, FIN-00029, Finland.
World J Gastroenterol. 2010 Dec 14;16(46):5845-51. doi: 10.3748/wjg.v16.i46.5845.
To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to anti-tumor necrosis factor-α (TNF-α) therapy.
Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α therapy. The individual stage of immune activation was studied applying our new in vitro assay, in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ), interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)]. The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α agent.
Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity i.e. CDEIS assessed before therapy (r = -0.621, P = 0.013 and r = -0.625, P = 0.013, respectively). FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r = -0.548, P = 0.034). Low serum induced FOXP3 (r = -0.600, P = 0.018) and GITR (r = -0.589, P = 0.021) expression and low IFNγ secretion from target cells (r = -0.538, P = 0.039) associated with treatment response detected as a decrease in CDEIS.
The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.
研究成人克罗恩病（CD）患者血清中的免疫激活阶段是否与疾病活动度以及抗肿瘤坏死因子-α（TNF-α）治疗的反应相关。
从 15 名接受抗 TNF-α 治疗的成人 CD 患者中获得血清样本。通过我们的新体外检测方法研究个体免疫激活阶段，在该方法中，用患者血清培养靶细胞（供体来源的外周血单核细胞），并使用效应[干扰素 γ（IFNγ）、白细胞介素（IL）-5]和调节性 T 细胞[叉头转录因子 3（FOXP3）和糖皮质激素诱导的肿瘤坏死因子受体（GITR）]的标志物研究患者血清诱导的 T 细胞激活。在接受抗 TNF-α 药物治疗前和 3 个月后，使用克罗恩病内镜严重程度指数（CDEIS）评估内镜疾病活动度。
在存在患者血清的情况下培养的靶细胞中 FOXP3 和 GITR 的诱导低与高疾病活动度相关，即治疗前的 CDEIS 评估（r = -0.621，P = 0.013 和 r = -0.625，P = 0.013）。FOXP3 表达与治疗前红细胞沉降率呈负相关（r = -0.548，P = 0.034）。低血清诱导的 FOXP3（r = -0.600，P = 0.018）和 GITR（r = -0.589，P = 0.021）表达以及靶细胞 IFNγ 分泌减少（r = -0.538，P = 0.039）与 CDEIS 降低相关，提示治疗反应。
在接受抗 TNF-α 治疗之前，患者血清中的免疫激活能力反映了肠道炎症和治疗反应。
