Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
Induction of arthritis by single monoclonal IgG anti-collagen type II antibodies and enhancement of arthritis in mice lacking inhibitory FcγRIIB
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DOI：
10.1002/eji.200323810
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发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Kleinau, S
中科院分区：
文献类型：
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作者：
Nandakumar, KS;Andrén, M;Kleinau, S
IgG抗II型胶原抗体（CII） （Ab）可诱导健康小鼠关节炎。在这里，我们研究了单克隆IgG抗cii Ab是否可以诱导cia易感的DBA/1小鼠关节炎，以及是否存在IgG亚类依赖性。通过比较DBA/1小鼠和FcgammaR缺陷小鼠的临床结果，研究了Fc受体IgG （FcgammaR）在抗cii抗体介导的关节炎中的作用。我们首次证实，针对DBA/1小鼠的单抗可诱导持续性关节炎。炎症关节的组织学显示大量细胞浸润，软骨和骨破坏。所有测试的IgG亚类（IgG1， IgG2a和IgG2b）都是致关节炎的，其中IgG1和IgG2b同型是主要的致关节炎的Ab。致病性依赖于激活FcgammaR，因为fgamma缺陷小鼠对Ab介导的关节炎完全耐药。IgG1和IgG2b Ab诱导的关节炎也受到FcgammaRIII破坏的抑制，而IgG2a Ab介导的关节炎则不受实质性影响。在缺乏FcgammaRIIB抑制的小鼠中，IgG1和IgG2b同型的关节炎反应进一步增强，而IgG2a Ab则没有。这些结果表明，单个抗cii抗体IgG可诱导糜糜性关节炎，而抗cii抗体IgG通过与FcgammaR结合介导关节炎。
IgG anti-collagen type II (CII) antibodies (Ab) can induce arthritis in healthy mice. Here we have investigated if single monoclonal IgG anti-CII Ab can induce arthritis in CIA-susceptible DBA/1 mice and if there is an IgG subclass dependency. The involvement of Fc receptors for IgG (FcgammaR) in anti-CII Ab-mediated arthritis was also investigated by comparing the clinical outcome in DBA/1 mice to those in FcgammaR-deficient mice. We demonstrate for the first time that single mAb to naive DBA/1 mice can induce persistent arthritis. Histology of the inflamed joints revealed massive cellular infiltrate and cartilage and bone destruction. All IgG subclasses tested (IgG1, IgG2a and IgG2b) were arthritogenic, with the IgG1 and IgG2b isotypes as the dominating arthritogenic Ab. Pathogenicity was dependent on engagement of activating FcgammaR, as FcRgamma-deficient mice were completely resistant to Ab-mediated arthritis. The arthritis induced with the IgG1 and IgG2b Ab was also inhibited by FcgammaRIII disruption, whereas arthritis mediated by the IgG2a Ab was not substantially affected. The arthritic response of the IgG1 and IgG2b isotypes, but not of the IgG2a Ab, was further enhanced in mice lacking the inhibitory FcgammaRIIB. These results demonstrate that single IgG anti-CII mAb can induce erosive arthritis and that IgG anti-CII Ab mediate arthritis by engagement of FcgammaR.