Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody-dependent cell-mediated cytotoxicity against pancreatic cancer cells
Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody-dependent cell-mediated cytotoxicity against pancreatic cancer cells
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DOI：
10.1111/j.1365-2249.2008.03726.x
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Bluth, M. H.
中科院分区：
文献类型：
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作者：
Fu, S. L.;Pierre, J.;Bluth, M. H.
除了过敏和寄生虫感染外，免疫球蛋白E （IgE）最近已被证明具有抗病毒和抗癌作用。我们研究了胰腺癌患者血清中IgE、其低亲和力受体、可溶性CD23 （sCD23）的水平以及IgE对胰腺癌细胞的作用。12例患者经影像学诊断为胰腺癌，活检证实为胰腺癌。15名健康志愿者作为对照。检测血清IgG （IgG, IgM, IgA, IgE）和sCD23水平（酶联免疫吸附法，比浊法），并评估癌症特异性IgE的存在（荧光显微镜，Western blot）。通过抗体依赖细胞介导的细胞毒性（ADCC）检测IgE的抗癌活性。与对照组相比，胰腺癌患者血清IgE和sCD23水平显著升高，而其他Ig同型（IgG, IgM, IgA）未观察到差异。流式细胞术和免疫荧光显微镜显示胰腺癌IgG和IgE的存在相似。然而，Western blot分析显示IgG和IgE抗原特异性抗体存在差异；IgE抗体识别一个50 kD的蛋白。ADCC研究表明，血清和纯化的IgE介导的对胰腺癌细胞的细胞毒性，这种作用被抗IgE中和抗体和IgE耗尽（免疫亲和）逆转；与健康对照相比，患者血清中的细胞毒性更大。这些数据表明，IgE和sCD23可能作为胰腺癌患者有用的生物标志物，并且在这种疾病的免疫反应中可能很重要，因为IgE定向治疗可能有助于指导治疗。
In addition to allergy and parasitic infections, immunoglobulin E (IgE) has been shown recently to possess anti-viral and anti-cancer effects. We investigated serum levels of IgE, its low-affinity receptor, soluble CD23 (sCD23) in patients with pancreatic cancer and the effect of IgE against pancreatic cancer cells. Twelve patients were evaluated for pancreatic cancer by imaging and confirmed by biopsy. Fifteen healthy volunteers served as controls. Serum Igs (IgG, IgM, IgA, IgE) and sCD23 levels were determined (enzyme-linked immunosorbent assay, nephelometry) and the presence of cancer-specific IgE was assessed (fluorescence microscopy, Western blot). IgE anti-cancer activity was determined by antibody-dependent cell-mediated cytotoxicity (ADCC). Serum levels of IgE and sCD23 were elevated significantly in patients with pancreatic cancer versus controls, whereas no differences were observed in other Ig isotypes (IgG, IgM, IgA). Flow cytometry and immunofluorescence microscopy demonstrated similar presence of IgG and IgE pancreatic cancer Igs. However, Western blot analysis indicated differences in IgG and IgE antigen-specific antibodies; IgE antibody recognized a 50 kD protein. ADCC studies demonstrated that serum and purified IgE-mediated cytotoxicity against pancreatic cancer cells, effects which were reversed with anti-IgE neutralizing antibody and IgE depletion (immunoaffinity); greater cytotoxicity was observed in patient serum when compared with healthy controls. These data suggest that IgE and sCD23 may serve as useful biomarkers for patients with pancreatic cancer and may be important in the immune response to this disease in that IgE-directed therapy may help to direct treatment.