Lindh Ingrid, Snir Omri, Lönnblom Erik, Uysal Hüseyin, Andersson Ida, Nandakumar Kutty Selva, Vierboom Michel, 't Hart Bert, Malmström Vivianne, Holmdahl Rikard
Arthritis Res Ther. 2014 Jul 8;16(4):R143. doi: 10.1186/ar4605.
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.
在类风湿关节炎（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动物中可检测到抗II型胶原（CII）抗体。我们之前使用来自关节炎小鼠的单克隆抗体表明，针对几种CII表位的特异性抗体具有致病性，尽管不同抗CII表位的作用在其他物种中尚未得到详细研究。因此，我们对RA患者与患有CIA的猴子和小鼠针对CII的自身抗体反应进行了种间比较研究。
使用CII三螺旋肽文库对CIA病程中的完整表位库进行分析。分析了RA患者血清和滑液以及恒河猴（猕猴）、普通狨猴（狨猴）和小鼠血清中对主要CII表位的抗体反应。
许多CII表位，包括主要的C1、U1和J1，与已确诊的CIA相关，精氨酸残基在抗CII抗体相互作用中起重要作用。主要表位在RA患者的血清中也能被识别，在滑液中更明显：77%的患者具有针对U1表位的抗体。抗CII免疫反应不限于抗瓜氨酸化蛋白抗体（ACPA）阳性的RA组。
CII构象依赖性抗体反应在RA中很常见，可能起源于类风湿关节，但与ACPA反应无相关性。重要的是，抗CII反应的精细特异性在猴子和啮齿动物的CIA中相似，其中识别的表位是保守的且具有主要致病作用。因此，抗CII抗体可能既是局部关节炎症的原因，也是其结果。
