类风湿关节炎抗IgG/CCP双特异自身抗体产生机制和意义研究

Reports showed that bispecific antibody (natural bispecific autoantibody) can be spontaneously produced under certain circumstances. In our preliminary experiments, a rabbit model that produced natural bispecific antibodies was established, and natural bispecific antibodies against cyclic citrullinated peptide (CCP) and immunoglobulin G (IgG) were also successfully identified in sera of RA patients. Given the structural differences between the natural bispecific autoantibody and the traditional autoantibody (i.e. monospecific antibody), differences in biological behavior are inevitably. So it is reasonable to speculate that the natural bispecific autoantibody may play a special role in the whole pathophysiological process of diseases. Based on these above-mentioned researches, our present study seek to investigate the production mechanism of the anti-IgG/CCP bispecific autoantibody in vivo and in vitro by means of enzyme-linked immunoassay, chromatography, mass spectrometry and genetic engineering, and further explore the pathophysiological role of the bispecific autoantibody in animal model and RA patients. Our study will be the first one to provide insights into the production mechanism of the bispecific autoantibody and its significance with regard to RA, and also lay the theoretical and practical foundation for further application of the natural bispecific autoantibody as a pivotal serum marker for RA.

研究表明，机体在某些特殊情况下可以自发产生双特异抗体（天然双特异抗体）。在前期实验中，我们构建了一种产生天然双特异抗体的兔模型，并在此基础上成功地在人类类风湿关节炎（RA）患者血清中鉴定出一种抗IgG分子和抗环瓜氨酸肽（CCP）的双特异自身抗体。由于双特异自身抗体与通常所指的自身抗体（单特异性）在结构上的差异，必然导致他们在生物学行为上的差异，因此双特异自身抗体可能在疾病的病理生理过程中发挥特殊生物学效能。本研究拟在前期研究基础上，采用酶联免疫分析、层析、质谱和基因工程等技术，分别从体内和体外研究抗IgG/CCP双特异自身抗体的产生机制，并进一步从动物模型和RA患者中探讨这种双特异自身抗体在RA中的病理生理学意义。以上研究将为揭示抗IgG/CCP双特异自身抗体在RA中的产生机制和意义提供首批资料，并为这种双特异自身抗体发展成一种新的RA血清学标志物奠定理论和实验基础。