Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
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DOI：
10.1016/j.imbio.2012.04.011
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发表时间：
2013-02-01
期刊：
影响因子：
2.8
通讯作者：
Skogh, Thomas
中科院分区：
文献类型：
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作者：
Svard, Anna;Kastbom, Alf;Skogh, Thomas
循环IgG抗环瓜氨酸肽抗体（CCP）对类风湿关节炎（RA）和预后不良具有高度特异性。血清伊加抗CCP发生在IgG阳性病例的一个子集中，并且与更具侵袭性的疾病有关。然而，粘蛋白IgA类抗体通常与抗炎作用和全身耐受诱导相关。在本研究中，未受刺激的唾液样本63例已建立RA和20名健康人进行了分析，通过酶联免疫测定伊加抗CCP抗体的存在。为了确保抗原特异性，分析了IgA与相应的未瓜氨酸化抗原环精氨酸肽（CAP）的反应性，并计算了抗CCP/抗CAP比值。通过医疗记录获得关于疾病活动和放射学结局的回顾性数据。在14/63例（22%）患者和1例（5%）对照中发现唾液伊加抗CCP（阳性试验=抗CCP/抗CAP比值> 1.5）。唾液伊加的反应性抑制剂量依赖性的预孵育与可溶性CCP的程度强烈相关的抗CCP/抗CAP的比例。在唾液伊加抗CCP阳性患者中，诊断后6年内关节糜烂明显较低（p = 0.043），并且在诊断时有降低红细胞沉降率（p = 0.071）和C反应蛋白（p = 0.085）的趋势。对比循环IgG和伊加抗CCP，我们的研究结果表明，唾液伊加抗体可能与RA的严重程度较低的结果。假设这与分泌型IgA类自身抗体对粘膜表面存在的瓜氨酸化抗原的抗炎和保护性免疫调节作用有关。(C)2012 Elsevier GmbH. All rights reserved.
Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio > 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces. (C) 2012 Elsevier GmbH. All rights reserved.