Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage.

Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage.
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DOI:
10.1186/s13075-015-0536-2
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发表时间:
2015-02-07
影响因子:
4.9
通讯作者:
Rantapää-Dahlqvist S
Rantapää-Dahlqvist S
中科院分区:
医学2区
文献类型:
--
作者:
Brink M;Verheul MK;Rönnelid J;Berglin E;Holmdahl R;Toes RE;Klareskog L;Trouw LA;Rantapää-Dahlqvist S

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在类风湿性关节炎(RA)中发现了一种新的自身抗体系统,即抗氨基甲酰化蛋白(抗CARP)抗体。在症状出现之前和之后随后发展为类风湿性关节炎的个体的样本中评估了抗鲤鱼抗体的存在,这些样本与先前分析的抗瓜氨酸多肽(ACPA特异性)和抗CCP2抗体有关。共有252名个人,423份来自RA症状出现前的样本,以及197名对照人群被确认为瑞典北部医学生物库的捐赠者;其中192人在诊断时也进行了抽样。所有样本均用ELISA法检测抗鲤鱼抗体和抗CCP2抗体。使用基于免疫CAP ISAC系统(Phadia)的定制微阵列分析了10种不同的针对瓜氨酸抗原(ACPA特异性)的抗体反应性。与对照组相比,症状前期个体血清中抗鲤鱼抗体浓度显著升高(P<0.001),发病后血清抗鲤鱼抗体水平也显著升高(P<0.001)。随着类风湿关节炎的发展,症状前期个体对抗鲤鱼抗体的敏感性分别为13.9%(95%CI:11~17.6)和42.2%(95%CI:35.4~49.3)。在抗CCP2或ACPA特异性阴性的个体中,抗鲤鱼抗体阳性率为5.1%~13.3%。抗鲤鱼抗体的存在与基线和24个月时的放射性破坏显著相关,也与放射变化有关(P<0.05,全部)。结果表明,抗CARP抗体与疾病的发展有关,即使在调整了不同ACPA的存在后,在抗CCP2阴性的个体中也是如此,并有助于识别独立于ACPA的疾病放射学进展较差的患者子集。本文的在线版本(doi:10.1186/s130750150536-2)包含补充材料,授权用户可以使用。
The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P <0.001) and also increased significantly after disease onset (P <0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P <0.05, all). The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA. The online version of this article (doi:10.1186/s13075-015-0536-2) contains supplementary material, which is available to authorized users.
DOI: 10.1186/ar1767
发表时间: 2005
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