St. Francis Hospital and Health Care Centers, Beech Grove, IN, USA.
Int J Cancer. 2010 Jul 15;127(2):491-6. doi: 10.1002/ijc.25038.
We and others have reported that multiple autoantibodies are unmasked in human polyclonal antibody preparations after exposure to physiological oxidizing agents (hemin) or electromotive force. We now have asked if oxidation unmasks autoantibody reactivities in monoclonal antibodies (mAb). To do this, we have studied 9 FDA approved mAb used therapeutically, including 4 chimeric, 4 humanized and 1 chemically modified chimeric Fab that were exposed to the physiological oxidizing agent hemin at 36 degrees C for 20 hr. These mAb were studied for autoantibody activity to phospholipids and DNA before and after oxidation with hemin and found to develop autoantibody activities after oxidation, while retaining their original specificity as measured by mAb anti-glycophorin A binding of erythrocytes, CD 19 binding to B lymphocytes and anti-HLA-A29 binding to A29-positive lymphocytes. The finding that certain mAb have the potential to unmask autoantibody activities as a consequence of exposure to physiological redox reactions in vitro gives pause to our present understanding of the immunological basis of tolerance and concern for potential autoimmune side effects in patients receiving mAb for diagnosis or treatment.
我们和其他人已经报道，在暴露于生理氧化剂（血红素）或电动势后，人类多克隆抗体制剂中会揭示出多种自身抗体。现在我们已经询问了氧化是否会在单克隆抗体（mAb）中揭示自身抗体反应。为此，我们研究了 9 种已获 FDA 批准用于治疗的 mAb，包括 4 种嵌合、4 种人源化和 1 种化学修饰的嵌合 Fab，这些 mAb 在 36°C 下暴露于生理氧化剂血红素 20 小时。在氧化和未氧化之前，这些 mAb 研究了对磷脂和 DNA 的自身抗体活性，发现氧化后会产生自身抗体活性，同时保持其原始特异性，如 mAb 与红细胞上的糖蛋白 A、B 淋巴细胞上的 CD19 和 A29 阳性淋巴细胞上的抗 HLA-A29 的结合所测量的。发现某些 mAb 有可能在体外暴露于生理氧化还原反应后揭示自身抗体活性，这使我们对耐受的免疫学基础和接受 mAb 进行诊断或治疗的患者潜在自身免疫副作用的担忧产生了停顿。
