Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice.
Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice.
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DOI：
10.1186/ar4605
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发表时间：
2014-07-08
影响因子：
4.9
通讯作者：
Holmdahl R
中科院分区：
文献类型：
--
作者：
Lindh I;Snir O;Lönnblom E;Uysal H;Andersson I;Nandakumar KS;Vierboom M;'t Hart B;Malmström V;Holmdahl R
在类风湿性关节炎 (RA) 患者以及患有胶原诱导性关节炎 (CIA) 的非人类灵长类动物和啮齿类动物中检测到 II 型胶原蛋白 (CII) 抗体。我们之前已经使用来自关节炎小鼠的单克隆抗体证明了对几种 CII 表位特异的抗体具有致病性，尽管不同的抗 CII 表位的作用尚未在其他物种中进行详细研究。因此，我们对 RA 患者与患有 CIA 的猴子和小鼠对 CII 的自身抗体反应进行了一项物种间比较研究。使用 CII 三螺旋肽文库对 CIA 病程中的完整表位库进行分析。对 RA 患者的血清和滑液以及恒河猴 (Macaca mulatta)、普通狨猴 (Callithrix jacchus) 和小鼠的血清中的主要 CII 表位的抗体反应进行了分析。许多 CII 表位（包括主要 C1、U1 和 J1）与已建立的 CIA 相关，并且精氨酸残基在抗 CII 抗体相互作用中发挥重要作用。主要表位也在 RA 患者中得到识别，在血清中甚至在滑液中更为明显：77% 的患者具有针对 U1 表位的抗体。抗 CII 免疫反应并不局限于抗瓜氨酸蛋白抗体 (ACPA) 阳性 RA 组。 CII 构象依赖性抗体反应在 RA 中很常见，可能源自类风湿关节，但未显示与 ACPA 反应相关。重要的是，抗 CII 反应的精细特异性与猴子和啮齿动物中的 CIA 相似，其中识别的表位是保守的并具有主要致病作用。因此，抗 CII 抗体既可能导致局部关节炎症，也可能是局部关节炎症的结果。
Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA. Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice. Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group. CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation.
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影响因子：
4.9
作者：
Mullazehi M;Wick MC;Klareskog L;van Vollenhoven R;Rönnelid J
通讯作者：
Rönnelid J
影响因子：
4.9
作者：
Vierboom, Michel P. M.;Breedveld, Elia;'t Hart, Bert A.
通讯作者：
't Hart, Bert A.
影响因子：
--
作者：
HOLMDAHL, R;RUBIN, K;WIGZELL, H
通讯作者：
WIGZELL, H
影响因子：
--
作者：
Snir, Omri;Widhe, Mona;Malmstrom, Vivianne
通讯作者：
Malmstrom, Vivianne
DOI：
10.1084/jem.20081862
发表时间：
2009-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Uysal H;Bockermann R;Nandakumar KS;Sehnert B;Bajtner E;Engström A;Serre G;Burkhardt H;Thunnissen MM;Holmdahl R
通讯作者：
Holmdahl R