Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity.
Arthrogenicity of type II collagen monoclonal antibodies associated with complement activation and antigen affinity.
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DOI：
10.1186/1476-9255-8-31
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发表时间：
2011-11-04
期刊：
影响因子：
--
通讯作者：
Yoshino S
中科院分区：
文献类型：
--
作者：
Koobkokkruad T;Kadotani T;Hutamekalin P;Mizutani N;Yoshino S
胶原抗体诱导关节炎（CAIA）模型是一种针对II型胶原（CII）的单克隆抗体（mab）鸡尾酒，已被广泛用于研究自身免疫性关节炎的发病机制。在本模型中，并非所有针对CII的单克隆抗体都能诱导关节炎，因为初始事件之一是在软骨表面或滑膜中形成胶原-抗体免疫复合物，随后复合物激活补体诱导关节炎，这表明具有较强结合小鼠CII和激活补体能力的单克隆抗体组合可能有效诱导小鼠关节炎。在本研究中，我们研究了IgG2a （CII-6和C2A-12）、IgG2b （CII-3、C2B-14和C2B-16）和抗牛或鸡CII单克隆抗体（mAb） IgM （CM-5）亚克隆联合诱导关节炎与单克隆抗体激活补体和结合小鼠CII的能力之间的关系。给DBA/1J小鼠注射几种单克隆抗体组合，然后再注射脂多糖。此外，ELISA检测了单克隆抗体激活补体和结合小鼠CII的能力。首先，给DBA/1J小鼠注射4单抗（CII-3、CII-6、C2B-14和CM-5），然后注射脂多糖，造成中度关节炎。排除其中一种单克隆抗体，即仅使用CII-3、CII-6和C2B-14，会引起更大的关节炎症。接下来，在这3种单克隆抗体中加入C2A-12而不加入C2B-16会产生更严重的关节炎。由全部5个单抗组成的5个克隆组合效果较差。组织学上，给予新开发的4克隆鸡尾酒的小鼠滑膜组织明显增生，炎症细胞大量浸润，软骨和骨严重破坏。此外，6个克隆中的4个（CII-3、CII-6、C2B-14和C2A-12）不仅与小鼠CII有强烈的交叉反应，而且在体外也有明显的补体活化。4个具有较强激活补体和结合小鼠CII能力的单抗组合有效地诱导了DBA/1J小鼠关节炎。这种体外系统可能有助于选择与关节炎发展相关的单克隆抗体。
The collagen antibody-induced arthritis (CAIA) model, which employs a cocktail of monoclonal antibodies (mAbs) to type II collagen (CII), has been widely used for studying the pathogenesis of autoimmune arthritis. In this model, not all mAbs to CII are capable of inducing arthritis because one of the initial events is the formation of collagen-antibody immune complexes on the cartilage surface or in the synovium, and subsequent activation of the complement by the complexes induces arthritis, suggesting that a combination of mAbs showing strong ability to bind mouse CII and activate the complement may effectively induce arthritis in mice. In the present study, we examined the relationship between the induction of arthritis by the combination of IgG2a (CII-6 and C2A-12), IgG2b (CII-3, C2B-14 and C2B-16) and IgM (CM-5) subclones of monoclonal antibodies (mAb) of anti-bovine or chicken CII and the ability of mAbs to activate complement and bind mouse CII. DBA/1J mice were injected with several combinations of mAbs followed by lipopolysaccharide. Furthermore, the ability of mAbs to activate the complement and bind mouse CII was examined by ELISA. First, DBA/1J mice were injected with the combined 4 mAbs (CII-3, CII-6, C2B-14, and CM-5) followed by lipopolysaccharide, resulting in moderate arthritis. Excluding one of the mAbs, i.e., using only CII-3, CII-6, and C2B-14, induced greater inflammation of the joints. Next, adding C2A-12 but not C2B-16 to these 3 mAbs produced more severe arthritis. A combination of five clones, consisting of all 5 mAbs, was less effective. Histologically, mice given the newly developed 4-clone cocktail had marked proliferation of synovial tissues, massive infiltration by inflammatory cells, and severe destruction of cartilage and bone. Furthermore, 4 of the 6 clones (CII-3, CII-6, C2B-14, and C2A-12) showed not only a strong cross-reaction with mouse CII but also marked activation of the complement in vitro. The combination of 4 mAbs showing strong abilities to activate the complement and bind mouse CII effectively induced arthritis in DBA/1J mice. This in vitro system may be useful for the selection of mAbs associated with the development of arthritis.
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影响因子：
3.6
作者：
Kuhn, Kristine A.;Cozine, Cassy L.;Holers, V. Michael
通讯作者：
Holers, V. Michael
影响因子：
15.3
作者：
STUART, JM;CREMER, MA;KANG, AH
通讯作者：
KANG, AH
影响因子：
--
作者：
Wouters, D;Voskuyl, AE;Hack, CE
通讯作者：
Hack, CE
影响因子：
5.4
作者：
Nandakumar, KS;Andrén, M;Kleinau, S
通讯作者：
Kleinau, S
影响因子：
4.6
作者：
Banda, N. K.;Levitt, B.;Arend, W. P.
通讯作者：
Arend, W. P.