High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibodycontaining immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset

High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibodycontaining immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset
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DOI:
10.1136/ard.2006.064782
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发表时间:
2007-04-01
影响因子:
27.4
通讯作者:
Ronnelid, Johan
Ronnelid, Johan
中科院分区:
医学1区
文献类型:
--
作者:
Mullazehi, Mohammed;Mathsson, Linda;Ronnelid, Johan

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目的:探讨较早报道的含有表面结合 II 型胶原 (CII) 的免疫复合物 (IC) 的细胞因子诱导特性是否具有临床影响。 方法:对 274 名早期类风湿性关节炎 (RA) 患者的抗 CII 血清学进行分析。针对抗CII IC诱导的肿瘤坏死因子(TNF)α、白细胞介素(IL)1β和IL8的水平,对抗CII水平升高的患者连续随访1-5年。将抗体和 IC 诱导的细胞因子水平与 5 年随访期间的临床指标进行比较。结果:100 名健康对照者中 5 名和 24 名 274 名 RA 患者(8.8%)表现出抗天然 CII 抗体水平升高(> 29 任意单位 (AU)/ml),但无显着差异。 9/ 274 (3.3%) 患有 RA 且无对照的患者组成了一个具有高抗 CII 水平 > 450 AU/ml 的离散组。这些高抗CII水平血清与体外形成的含有抗CII的IC诱导促炎细胞因子相关。 8/ 9 具有高基线抗 CII 水平的患者表现出抗体水平、IC 诱导的细胞因子、C 反应蛋白 (CRP) 和红细胞沉降率 (ESR) 平行下降。抗 CII 阳性患者的 CRP 和 ESR 水平在基线时显着升高,但在随访后期没有显着升高。结论:抗天然 CII 阳性 RA 患者具有独特的临床表型,其特征是早期急性期反应,可能是由关节软骨中含有抗 CII 的 IC 驱动的。
Objective: To investigate whether the cytokine- inducing properties of surface- bound collagen type II ( CII)- containing immune complexes ( IC), which were reported earlier, have any clinical impact.Methods: Anti- CII serology was analysed in 274 patients with early rheumatoid arthritis ( RA). Patients with increased levels of anti- CII were followed serially for 1 - 5 years with regard to anti- CII IC- induced levels of tumour necrosis factor ( TNF)alpha, interleukin ( IL) 1 beta and IL8. Levels of antibodies and IC- induced cytokines were compared with clinical indices over 5 years of follow- up.Results: 5/ 100 healthy controls and 24/ 274 ( 8.8%) patients with RA exhibited increased levels (> 29 arbitrary units ( AU)/ ml) of anti- native CII antibodies, a non- significant difference. 9/ 274 ( 3.3%) patients with RA and no controls comprised a discrete group with high anti- CII levels > 450 AU/ ml. These high anti- CII level sera were associated with induction of proinflammatory cytokines by anti- CII- containing IC formed in vitro. 8/ 9 patients with high baseline anti- CII levels exhibited a parallel decline in antibody levels, IC- induced cytokines, C reactive protein ( CRP) and erythrocyte sedimentation rate ( ESR). Anti- CII- positive patients had significantly increased levels of CRP and ESR at baseline, but not later during the follow- up.Conclusions: Anti- native CII- positive patients with RA have a distinct clinical phenotype characterised by an early acute phase response that might be driven by anti- CII- containing IC in joint cartilage.