Suppression of Collagen-Induced Arthritis in Mice by Anti-Collagen Antibody Fab Fragments
Suppression of Collagen-Induced Arthritis in Mice by Anti-Collagen Antibody Fab Fragments
复制标题
抗胶原抗体 Fab 片段抑制小鼠胶原诱导的关节炎
DOI：
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
N. Mizutani
中科院分区：
文献类型：
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作者：
S. Yoshino;R. Maktrirat;N. Mizutani
Fab片段（Fab）保持与特异性抗原的结合能力，但缺乏在风湿性关节炎（RA）中起关键作用的补体和白细胞上的受体的结合位点。在本研究中，我们研究了通过木瓜蛋白酶消化抗CII抗体制备的抗CII Fab是否抑制小鼠II型胶原（CII）诱导的关节炎（CIA）。用鸡CII和完全弗氏佐剂免疫DBA/1 J小鼠诱导CIA。为了研究抗CII Fab对CIA模型的作用，在第一次免疫前1天腹膜内注射抗CII Fab。结果，CIA被抗CII Fab显著抑制;此外，抗CII Fab未处理的小鼠的组织学特征包括严重增生滑膜、软骨和关节破坏以及白细胞浸润，而给予抗CII Fab的动物显示这些组织学变化显著减少。此外，抗CII Fab对CIA的抗原特异性抑制与血清中补体C3 a水平降低有关。同时，体外研究显示，抗CII Fab显著阻断完整抗CII抗体的结合，并且还降低补体活化。总的来说，CIA的发展受到抗CII Fab的抑制，这阻止了抗CII抗体与抗原的结合，随后抑制了补体活化，表明自身免疫性关节炎疾病如RA可以用致病性抗体Fab特异性治疗。
Fabs fragments (Fabs) maintain binding ability to specific antigens, but lack the binding site for complements and for receptors on leukocytes that play a crucial role in Rheumatoid Arthritis (RA). In the present study, we investigated whether type II Collagen (CII)-Induced Arthritis (CIA) in mice was suppressed by anti-CII Fabs prepared by papain digestion of anti-CII antibodies. CIA was induced in DBA/1J mice by immunization with chicken CII and completes Freund’s adjuvant. To investigate the effect of anti-CII Fabs on the CIA model, mice were injected intraperitoneally with anti-CII Fabs 1 day before the first immunization. As a result, CIA was markedly inhibited by anti-CII Fabs; furthermore, the histological features of anti-CII Fabs-untreated mice included severe hyperplatic synnovium, cartilage and joint destruction, and leukocytic infiltration, whereas animals given anti-CII Fabs showed significant reduction of these histological changes. Additionally, antigen-specific suppression of CIA by anti-CII Fabs was related to the reduced levels of complement C3a in serum. Meanwhile, in vitro studies revealed that anti-CII Fabs significantly blocked the binding of intact anti-CII antibodies and also decreased complement activation. Collectively, the development of CIA was suppressed by anti-CII Fabs, which prevented the binding of anti-CII antibodies to antigen followed by the inhibition of complement activation, suggesting that autoimmune arthritic diseases such as RA may be specifically treated with pathogenic antibody Fabs.
影响因子：
4.4
作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart
通讯作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart