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首页> 外文期刊>International journal of colorectal disease. >Down-regulation of interferon-gamma parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study.
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Down-regulation of interferon-gamma parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study.

机译：炎症性肠病患者中干扰素-γ的下调与对选择性白细胞单采的临床反应相似：一项为期12个月的随访研究。

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BACKGROUND & AIMS: Pilot studies have indicated a therapeutic role for an apheresis device (Adacolumn) that selectively adsorbs leukocytes in patients with inflammatory bowel diseases. It may also exert immunoregulatory effects contributing to its clinical efficacy. This study aimed to correlate the clinical response to leukocyte apheresis with the expression of key cytokines in mucosal tissue, in peripheral leukocytes, and in plasma. METHODS: Ten patients (seven with Crohn's disease and three with ulcerative colitis, median age: 31 years) with mild to moderately chronic activity were recruited to an open study. Patients were refractory to or had a relapse despite conventional treatment including azathioprine. Leukocyte apheresis was performed once a week for five consecutive weeks. Clinical efficacy was assessed on week 7 and after 12 months. Colonoscopy with multiple biopsies was performed at the start of the study and after 7 weeks for semiquantitative immunohistochemical analyses of cytokines. Cytokine levels in blood and the proportion of cytokine producing CD4+ and CD8+ lymphocytes were determined. RESULTS: The apheresis procedures were well tolerated and no major adverse events were encountered. The median clinical activity score decreased from 12 to 7 on week 7 (P=0.031, n=9) and to 4 after 12 months (P=0.004, n=9). Five patients were in clinical remission at the 12th month. Tissue interferon (IFN)-gamma-positive T-cells decreased in clinical responders (P=0.027) after apheresis. In parallel, significantly lower levels of IFN-gamma-producing lymphocytes were detected in peripheral blood. IFN-gamma-positive cells in pretreatment biopsies completely disappeared or decreased in posttreatment biopsies sampled on week 7 in responders (P=0.027) and appeared to predict the maintenance of long-term remission or response after 12 months. CONCLUSIONS: Leukocyte apheresis is a novel and safe nonpharmacological adjunct therapy that may prove useful in steroid refractory or dependent patients when conventional drugs have failed. Down-regulation of IFN-gamma in mucosal biopsies and in peripheral leukocytes may be a predictive marker for sustained, long-term response.
机译：背景与目的：初步研究表明，单采血液分离设备（Adacolumn）的治疗作用可选择性吸收炎症性肠病患者的白细胞。它还可能发挥免疫调节作用，从而提高其临床疗效。这项研究旨在将对白细胞单采的临床反应与粘膜组织，外周白细胞和血浆中关键细胞因子的表达联系起来。方法：招募了10例轻度至中度慢性活动的患者（七例患有克罗恩氏病，三例患有溃疡性结肠炎，中位年龄：31岁）参加了一项开放研究。尽管包括硫唑嘌呤在内的常规治疗，患者仍难治或复发。每周进行一次白细胞单采，连续五周。在第7周和12个月后评估临床疗效。在研究开始时和7周后进行多次活检的结肠镜检查，以进行细胞因子的半定量免疫组织化学分析。测定血液中的细胞因子水平和产生细胞因子的CD4 +和CD8 +淋巴细胞的比例。结果：血液分离程序耐受良好，未遇到重大不良事件。中位临床活动评分从第7周的12降至7（P = 0.031，n = 9），并在12个月后降至4（P = 0.004，n = 9）。在第12个月有5例患者临床缓解。血液分离后临床应答者的组织干扰素（IFN）-γ阳性T细胞减少（P = 0.027）。同时，在外周血中检测到明显降低的产生IFN-γ的淋巴细胞水平。应答者在第7周采样的治疗后活检样本中，治疗前活检样本中的IFN-γ阳性细胞完全消失或减少（P = 0.027），似乎可预测12个月后长期缓解或反应的维持。结论：白细胞单采是一种新颖且安全的非药物辅助疗法，当常规药物治疗失败时，可用于类固醇难治性或依赖患者。粘膜活检和外周血白细胞中IFN-γ的下调可能是持续长期反应的预测指标。

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