Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis
Type I interferons have no major influence on humoral autoimmunity in rheumatoid arthritis
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DOI：
10.1093/rheumatology/kep345
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发表时间：
2010-01-01
期刊：
影响因子：
5.5
通讯作者：
Baeten, Dominique L.
中科院分区：
文献类型：
--
作者：
Cantaert, Tineke;van Baarsen, Lisa G.;Baeten, Dominique L.
Objective. I型干扰素最近与自身抗体介导的疾病（例如系统性红斑狼疮）有关。由于一半的RA患者显示I型IFN高信号，我们在一项初步研究中调查了I型IFN是否决定RA中的自身抗体应答。从52例RA患者中获得血清和外周血细胞，其中21例患者在英夫利西单抗治疗前后配对样本。从8名无关节炎的抗瓜氨酸化蛋白抗体（ACPA）阳性个体和10名ACPA阴性健康对照中采集了额外的样本。通过外周血细胞基因表达分析和定量RT-PCR确定I型IFN特征。ELISA法检测ACPA IgG、IgM、RF IgM、抗核小体IgM、抗dsDNA。在活动性疾病期间，I型IFN签名与ACPA和RF的存在和滴度无关。TNF阻断诱导的ANA升高相似，两组RF滴度降低相似。ACPA IgG和IgM水平出现下调，只有在I型IFN低组。这些变化与TNF阻断后I型IFN应答基因活性的变化无关。此外，在没有关节炎和炎症的个体中，ACPA反应与I型IFN的增加无关。在这项探索性研究中，I型IFN信号似乎对RA的体液自身免疫反应没有重大影响。这些数据的复制仍然是必要的。
Objective. Type I IFNs have recently been implicated in autoantibody-mediated diseases such as SLE. As half the RA patients display a type I IFN high signature, we investigated in a pilot study if type I IFN determines the autoantibody response in RA.Methods. Serum and peripheral blood cells were obtained from 52 RA patients, with paired samples before and after infliximab treatment in 21 patients. Additional samples were collected from 8 anti-citrullinated protein antibody (ACPA)-positive individuals without arthritis and from 10 ACPA-negative healthy controls. The type I IFN signature was determined by peripheral blood cell gene expression analysis and quantitative RT-PCR. ACPA IgG and IgM, RF IgM, anti-nucleosome IgM and anti-dsDNA were measured by ELISA.Results. The type I IFN signature was not related to the presence and titers of ACPA and RF during active disease. TNF blockade induced a similar rise of ANAs, and a similar decrease in RF titers in both groups. ACPA IgG and IgM levels appeared to be down-modulated only in the type I IFN low group. These changes were independent of the changes in type I IFN response gene activity after TNF blockade. Furthermore, the ACPA response in individuals without arthritis and inflammation was not related to an increase of type I IFN.Conclusions. In this explorative study, type I IFN signature does not appear to have a major impact on the humoral autoimmune response in RA. Replication of these data remains warranted.