Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis
Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis
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DOI：
10.1016/j.jim.2005.06.017
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发表时间：
2005-09-01
影响因子：
2.2
通讯作者：
Holmdahl, R
中科院分区：
文献类型：
--
作者：
Nandakumar, KS;Holmdahl, R
对位于II型胶原（CII）的三螺旋部分上的限定表位的抗体应答与胶原诱导的关节炎（CIA）和类风湿性关节炎（RA）的发展相关。针对与关节炎相关的表位的单克隆抗体，而不是针对与关节炎无关的表位的特异性抗体，在小鼠中诱导关节炎，即所谓的胶原抗体诱导的关节炎（CAIA）模型。我们已经选择了对三螺旋CII上的四个明确定义的主要表位（C1、J1、D3和U1表位）特异的单克隆IgG抗体。这些抗体特异性结合表位，如使用重组或合成的三螺旋表位所确定的。它们由体细胞突变的V基因编码。它们都在正常小鼠体内结合软骨。所有的抗体在静脉注射后诱导轻度关节炎，如果作为鸡尾酒注射，它们诱导严重的临床关节炎。静脉内注射总共4mg抗体（每个克隆0.5mg抗体）在几种不同的小鼠品系中诱导关节炎，而没有任何二次免疫刺激，7天后腹膜内注射LPS显著提高了严重程度。因此，该方法被推荐为诱导CAIA的新方案。(c)2005 Elsevier B.V.保留所有权利。
An antibody response to defined epitopes located on the triple helical portion of type II collagen (CII) is associated with the development of collagen-induced arthritis (CIA) and rheumatoid arthritis (RA). Monoclonal antibodies to epitopes associated with arthritis, but not antibodies specific for epitopes not associated with arthritis, induce arthritis in mice, the so-called collagen antibody induced arthritis (CAIA) model. We have selected monoclonal IgG antibodies specific for four well-defined major epitopes on triple helical CII, the Cl, Jl, D3 and Ul epitopes. These antibodies bind the epitopes specifically as determined using recombinant or synthetic triple helical epitopes. They are encoded from somatically mutated V genes. They all bind cartilage m vivo in normal mice. All of the antibodies induce mild arthritis after injection intravenously and if injected as a cocktail they induce severe clinical arthritis. Intravenous injection of a total of 4 mg antibodies (0.5 mg antibodies per clone) induced arthritis in several different mouse strains without any secondary immune stimulus and intraperitoneal injection of LPS 7 days later dramatically raised the severity. Thus, this method is recommended as a new protocol for the induction of CAIA. (c) 2005 Elsevier B.V. All rights reserved.