Complement receptor CR2/CR1 deficiency protects mice from collagen-induced arthritis and associates with reduced autoantibodies to type II collagen and citrullinated antigens
Complement receptor CR2/CR1 deficiency protects mice from collagen-induced arthritis and associates with reduced autoantibodies to type II collagen and citrullinated antigens
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DOI：
10.1016/j.molimm.2008.01.036
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Holers, V. Michael
中科院分区：
文献类型：
--
作者：
Kuhn, Kristine A.;Cozine, Cassy L.;Holers, V. Michael
胶原诱导性关节炎(CIA)是自身免疫性炎症性关节炎的一种模型，依赖于补体激活和有效的B细胞反应。为了确定补体受体CR2/CR1在CIA中的重要性，将Cr2-/-基因回交到DBA/1J品系。在第0天和第21天，用牛II型胶原免疫CIA，诱导出CIA。CR2-/-小鼠的关节炎严重程度显著减轻，牛胶原和鼠胶原抗体显著降低，瓜氨酸抗原抗体显著降低。抗瓜氨酸抗原的自身抗体已被证明可以放大抗II型胶原被动转移性关节炎。为了验证这样的假设，即简单地替换这些抗体可能会在Cr2-/-小鼠中重新建立严重的疾病，在疾病过程中给小鼠注射了抗瓜氨酸抗原的单抗。虽然这些抗体靶向的瓜氨酸抗原存在于所有小鼠的关节中，但这些单抗的加入只增加了Cr2+/+小鼠的疾病严重性。综上所述，这些数据表明，在CIA模型中，CR2/CR1是形成强大的自身免疫所必需的，而抗瓜氨酸抗原抗体对关节炎的放大依赖于关节炎Cr2-/-小鼠中缺失的因子(S)。(C)2008爱思唯尔有限公司。保留所有权利。
Collagen-induced arthritis (CIA), a model of autoimmune inflammatory arthritis, depends upon complement activation and effective B cell responses. To determine the importance of complement receptors CR2/CR1 in CIA, the Cr2-/- genotype was backcrossed onto the DBA/1j strain. CIA was induced by immunization with bovine type II collagen in CIA on days 0 and 21. Cr2-/- mice demonstrated a significantly diminished arthritis severity, decreased antibodies to bovine and murine collagen, and a significant reduction in antibodies to citrullinated antigens. Autoantibodies to citrullinated antigens have been shown to amplify anti-type II collagen passive transfer arthritis. To test the hypothesis that that simple replacement of such antibodies might re-establish severe disease in Cr2-/- mice, monoclonal antibodies to citrullinated antigens were administered to mice during the disease course. Although citrullinated antigens targeted by these antibodies were present within the joints of all mice, addition of these monoclonal antibodies increased disease severity only in Cr2+/+ mice. Taken together, these data suggest that CR2/CR1 are required to develop robust autoimmunity in the CIA model and that amplification of arthritis by antibodies to citrullinated antigens depends on factor(s) absent in arthritic Cr2-/- mice. (c) 2008 Elsevier Ltd. All rights reserved.