Omersel J, Jurgec I, Cucnik S, Kveder T, Rozman B, Sodin-Semrl S, Bozic B
University Medical Centre, Division of Internal Medicine, Department of Rheumatology, Vodnikova 62, SI-1000 Ljubljana, Slovenia.
Autoimmun Rev. 2008 Jul;7(7):523-9. doi: 10.1016/j.autrev.2008.04.005. Epub 2008 Apr 30.
Oxidation reactions can modify protein activity or specificity. Recently, a novel redox-reactive family of autoantibodies was described, which indicated involvement of altered antibodies (beside altered antigens) into autoimmune reactions. The aim of our study was to determine the binding capacity alterations of electro-oxidized blood donors' IgGs, and to evaluate their effects on released proinflammatory interleukin 6 in HUVEC.
We found out that 1.) Isolated blood donor IgGs bound after electro-oxidation to beta2-glycoprotein I, cardiolipin, citrullinated cyclic peptide and protein 3 by enzyme-linked immunosorbent assay, extractable nuclear antigens by counterimmuno-electrophoresis, and cell antigens by indirect immunofluorescence; 2.) Alterations in immunoreactivity of IgGs due to oxidation highly depend on electric current, time of exposure and the presence of antioxidants, 3.) Treatment of HUVEC with oxidized IgGs resulted in changed cell morphology, accompanied by an increase in released interleukin-6.
Our data suggest repeatable transformation of antibodies present in the blood of healthy persons and patients. Inter-individual differences in chemical stability of antibodies, patient's antioxidant status, and the microenvironmental changes at the cellular level may influence the range of antibody alterations and their involvement in pathophysiological autoimmune processes.
氧化反应可改变蛋白质活性或特异性。最近，描述了一类新型的氧化还原反应性自身抗体，这表明改变的抗体（除了改变的抗原）参与了自身免疫反应。我们研究的目的是确定电氧化的献血者免疫球蛋白G（IgG）的结合能力变化，并评估其对人脐静脉内皮细胞（HUVEC）中释放的促炎白细胞介素6的影响。
我们发现：1. 通过酶联免疫吸附测定法，电氧化后的分离献血者IgG与β2-糖蛋白I、心磷脂、瓜氨酸化环肽和蛋白3结合；通过对流免疫电泳与可提取核抗原结合；通过间接免疫荧光与细胞抗原结合；2. IgG免疫反应性因氧化而产生的变化高度依赖于电流、暴露时间和抗氧化剂的存在；3. 用氧化的IgG处理HUVEC导致细胞形态改变，同时释放的白细胞介素-6增加。
我们的数据表明健康人和患者血液中存在的抗体可发生重复性转变。抗体化学稳定性的个体差异、患者的抗氧化状态以及细胞水平的微环境变化可能会影响抗体改变的范围及其参与病理生理自身免疫过程的情况。
