Ishihara Shunji, Shoda Tetsuo, Ishimura Norihisa, Ohta Shoichiro, Ono Junya, Azuma Yoshinori, Okimoto Eiko, Izuhara Kenji, Nomura Ichiro, Matsumoto Kenji, Kinoshita Yoshikazu
Department of Gastroenterology and Hepatology, Shimane University School of Medicine, Japan.
Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Japan.
Intern Med. 2017 Nov 1;56(21):2819-2825. doi: 10.2169/internalmedicine.8763-16. Epub 2017 Sep 25.
Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3β/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.
目的 目前尚无用于诊断和监测嗜酸性粒细胞性胃肠疾病的临床实用血清生物标志物。本研究旨在探讨嗜酸性粒细胞相关蛋白作为血清生物标志物的潜在价值。方法 检测了29例嗜酸性粒细胞性胃肠疾病患者和80例对照者血清中49种细胞因子、趋化因子及其他蛋白质的浓度。结果 先前报道的可能作为嗜酸性粒细胞性食管炎生物标志物的白细胞介素(IL)-5、IL-33、嗜酸性粒细胞趋化因子-3和胸腺基质淋巴细胞生成素(TSLP)在血清中并未显著升高。相反,嗜酸性粒细胞性食管炎患者以及嗜酸性粒细胞性胃肠炎患者的B细胞趋化因子(BCA)-1/趋化因子(C-X-C基序)配体(CXCL)13和血液滤过C-C趋化因子(HCC)-1/CC趋化因子配体(CCL)14α水平显著升高,而粒细胞趋化蛋白(GCP)-2/CXCL6水平则受到抑制。皮肤T细胞趋化因子(CTACK)/CCL27、基质细胞衍生因子(SDF)-1/CXCL12、巨噬细胞炎性蛋白(MIP)-3β/CCL19和鳞状细胞癌抗原(SCCA)2水平仅在嗜酸性粒细胞性食管炎患者中升高。然而,患者组和对照组的数据存在大量重叠,表明这些血清生物标志物在目前可用的检测系统中对临床应用而言敏感性不足。结论 在研究的49种血清蛋白中,没有一种被证明对作为嗜酸性粒细胞性胃肠疾病诊断或监测的生物标志物具有足够的敏感性。