High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis
High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis
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DOI：
10.1371/journal.pone.0082300
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发表时间：
2013-12-18
期刊：
影响因子：
3.7
通讯作者：
Wilson, Keith T.
中科院分区：
文献类型：
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作者：
Coburn, Lori A.;Horst, Sara N.;Wilson, Keith T.
需要准确和高通量的技术来鉴定新的治疗靶点和优化炎症性肠病的治疗。我们的目的是评估使用Luminex技术的基于多分析物蛋白质的细胞因子/趋化因子测定。我们已经报道了基于Luminex的分析在评估葡聚糖硫酸钠结肠炎小鼠模型对L-精氨酸治疗的反应中是有用的。因此，我们研究了前瞻性收集的样本，从溃疡性结肠炎（UC）患者和对照组。从接受结肠镜检查的受试者中获得血清、结肠活检和临床信息，以评价UC或非UC适应症。共有38名正常对照和137名UC病例完成了研究。评估组织学疾病严重程度和马约疾病活动指数（DAI）。通过基于Luminex的42种分析物的多重检测来测量血清和结肠组织细胞因子/趋化因子谱。与对照组相比，组织学活动性UC患者血清中仅嗜酸性粒细胞趋化因子-1和G-CSF升高。虽然与对照相比，组织中的13种细胞因子/趋化因子在活动性UC中增加，但在血清和组织中的所有水平的活动性疾病中仅嗜酸细胞活化趋化因子-1增加。在组织中，Eotaxin-1与DAI和嗜酸性粒细胞计数相关。通过实时PCR证实了eotaxin-1水平的增加。组织嗜酸性粒细胞趋化因子-1水平也增加了实验小鼠结肠炎诱导的葡聚糖硫酸钠，恶唑酮，或柠檬酸杆菌啮齿类，但不是在小鼠幽门螺杆菌感染。我们的数据表明，嗜酸性粒细胞趋化因子-1作为UC的致病因素和治疗靶点，并表明基于Luminex的测定可能有助于评估IBD发病机制和选择患者进行抗细胞因子/趋化因子治疗。
Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies.