Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Rheumatology (Oxford). 2010 Jan;49(1):156-66. doi: 10.1093/rheumatology/kep345. Epub 2009 Nov 23.
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.
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.
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.
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.
Ⅰ型干扰素最近被牵连到自身抗体介导的疾病中，如 SLE。由于一半的 RA 患者表现出Ⅰ型干扰素（高）特征，我们在一项初步研究中调查了Ⅰ型干扰素是否决定了 RA 的自身抗体反应。
从 52 例 RA 患者中获得血清和外周血细胞，其中 21 例患者在接受英夫利昔单抗治疗前后有配对样本。从 8 名无关节炎的抗瓜氨酸蛋白抗体（ACPA）阳性个体和 10 名 ACPA 阴性健康对照者中收集了额外的样本。通过外周血细胞基因表达分析和定量 RT-PCR 来确定Ⅰ型干扰素特征。通过 ELISA 测量 ACPA IgG 和 IgM、RF IgM、抗核小体 IgM 和抗 dsDNA。
Ⅰ型干扰素特征与疾病活动期 ACPA 和 RF 的存在和滴度无关。TNF 阻断诱导了 ANA 的相似增加，并且在两组中 RF 滴度的相似下降。仅在Ⅰ型干扰素（低）组中，ACPA IgG 和 IgM 水平似乎被下调。这些变化与 TNF 阻断后Ⅰ型干扰素反应基因活性的变化无关。此外，无关节炎和炎症的个体中的 ACPA 反应与Ⅰ型干扰素的增加无关。
在这项探索性研究中，Ⅰ型干扰素特征似乎对 RA 中的体液自身免疫反应没有重大影响。仍然需要复制这些数据。
