Importance of CXCL16 as a biomarker for granulocytapheresis in patients with Crohn's disease
Importance of CXCL16 as a biomarker for granulocytapheresis in patients with Crohn's disease
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CXCL16 作为克罗恩病患者粒细胞分离术生物标志物的重要性
DOI：
10.1002/ibd.21657
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发表时间：
2011
影响因子：
4.9
通讯作者：
Chiba T
中科院分区：
文献类型：
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作者：
Nakase H;Uza N;Matsuura M;Chiba T
编辑：根据炎症性肠病(IBD)的病理生理学识别生物标记物是非常重要的。因此，对细胞因子和趋化因子的研究使我们能够找到候选分子作为IBD的治疗靶点和疾病活动性。CXCL16表达于抗原提呈细胞(APC)表面，包括CD14单核/巨噬细胞亚群和CD19 B细胞亚群。CXCL16通过APC介导革兰氏阳性和阴性细菌的黏附和吞噬，并作为一种趋化因子对表达CXCR6的细胞具有生物活性。因此，CXCL16在先天免疫和获得性免疫中都发挥着重要作用。我们非常感兴趣地注意到Diegelmann等人的《趋化因子CXCL16在克罗恩病和肠炎症模型中的表达和调节》。2在本文中，他们报道了CXCL16-CXCR6趋化因子-配体受体系统在肠道炎症中的重要性，活动期克罗恩病(CD)患者血清CXCL16水平显著高于对照组，而缓解期CD患者血清CXCL16水平与对照组无显著差异。考虑到CXCL16-CXCR6趋化因子系统参与Th1介导的炎症反应，我们推测该系统可能是CD患者疾病活动性的有用生物标志物。采用Adacolum(日本免疫研究实验室，日本高崎)的粒细胞分离术(GMA)治疗IBD患者的疗效和安全性一直受到关注，因为该系统有望成为一种天然的生物疗法，即选择性地从外周血中清除粒细胞和单核/巨噬细胞，导致炎性细胞因子如肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和白介素8(IL-8)的产生减少。3事实上，有几个关于GMA对CD4，5患者的疗效的报道；然而，GMA的确切机制仍不清楚。在这项研究中，我们首先评估了CXCL16是否可以作为GMA治疗CD患者疗效的生物标志物。从2009年到2010年，10名CD患者(8名男性，2名女性；平均年龄29岁)在常规治疗期间复发，包括皮质类固醇、硫唑嘌呤(AZA)和英夫利昔单抗，他们接受了GMA治疗。5例仅有结肠病变，2例仅有小肠病变，3例同时有小肠和大肠病变。克隆氏疾病活动指数(CDAI)平均265 6 33分。每个患者每周接受一次或两次GMA治疗，持续5周。在GMA治疗结束后评估临床反应。CDAI较基础值下降70分以上的患者视为有效。临床缓解定义为CDAI<；150。采用明尼阿波利斯R&D系统公司生产的人CXCL16定量酶联免疫吸附试剂盒(R&D Systems，Minneapolis，MN)检测血清CXCL16水平的变化。京都大学医院伦理委员会批准了该研究方案。10名患者中有6名(60%)被认为是应答者。在六名应答者中，有四名患者在GMA结束时病情缓解。其余4例患者临床症状未见改善。在GMA治疗结束时，所有患者的平均CDAI从265降至170。另外--
To the Editor: To identify biomarkers based on the pathophysiology of inflammatory bowel disease (IBD) is very important. Therefore, the study of cytokines and chemokines allowed us to find candidate molecules as a therapeutic target and disease activity of IBD. CXCL16 is expressed on the surface of antigen-presenting cells (APCs), including subsets of CD14 monocytes/macrophages and CD19 B cells. CXCL16 mediates adhesion and phagocytosis of both Gram-positive and-negative bacteria by APC and has a biologic activity as a chemokine for CXCR6-expressing cells. 1 Thus, CXCL16 plays an important role in both innate and adaptive immunity. We note with great interest ‘‘Expression and regulation of the chemokine CXCL16 in Crohn’s disease and models of intestinal inflammation’’by Diegelmann et al. 2 In this article, they reported the importance of CXCL16-CXCR6 chemokine-ligand receptor system in intestinal inflammation, and CXCL16 serum levels in patients with active Crohn’s disease (CD) were significantly higher compared with the control population, whereas CXCL16 serum levels in CD patients in remission were not significantly different from the control. Considering the involvement of the CXCL16-CXCR6 chemokine system in Th1-mediated inflammation, we speculated that this system could be a useful biomarker of disease activity for patients with CD.Therapeutic effect and safety of granulocytapheresis (GMA) using an Adacolumn (Japan Immunoresearch Laboratories, Takasaki, Japan) on patients with IBD has been much focused on because this system can be expected to be a natural biological therapy, in that selectively removing granulocytes and monocytes/macrophages from peripheral blood leads to decreasing production of inflammatory cytokines such as tumor necrosis factor alpha (TNF-a), interleukin (IL)-6, and IL-8. 3 In fact, there were several reports on the efficacy of GMA in patients with CD4, 5; however, the precise mechanism of GMA is still unclear. In this study we first evaluated whether or not CXCL16 could be a biomarker of the therapeutic effect of GMA on patients with CD. From 2009 to 2010, 10 patients with CD (eight male, two female; mean age 29 years) who had relapsed during conventional therapy including corticosteroids, azathioprine (AZA), and infliximab were treated with GMA. Five patients had only colonic lesions, two patients had small intestinal lesions alone, and three patients had both small and large intestinal lesions. The mean Crohn’s Disease Activity Index (CDAI) score was 265 6 33. Each patient received once or twice GMA per week for 5 weeks. The clinical response was assessed after the end of GMA. Patients with a decrease of more than 70 points in CDAI from the basal value were considered responders. Clinical remission was defined as CDAI< 150. In addition, the change of serum level of CXCL16 was evaluated by the human CXCL16 Quantikine Elisa Kit (R&D Systems, Minneapolis, MN). The study protocol was approved by the Kyoto University Hospital Ethics Committee. Six (60%) of 10 patients were considered responders. Of six responders, four patients went into remission at the end of GMA. The remaining four patients did not achieve clinical improvement. The mean CDAI for all patients decreased from 265 to 170 at the end of GMA therapy. In addi-