Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression.

Prevalence of interferon type I signature in CD14 monocytes of patients with Sjogren's syndrome and association with disease activity and BAFF gene expression.
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DOI:
10.1136/annrheumdis-2012-201381
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发表时间:
2013-05
影响因子:
27.4
通讯作者:
Versnel MA
Versnel MA
中科院分区:
医学1区
文献类型:
--
作者:
Brkic Z;Maria NI;van Helden-Meeuwsen CG;van de Merwe JP;van Daele PL;Dalm VA;Wildenberg ME;Beumer W;Drexhage HA;Versnel MA

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确定69例原发性干燥综合征(pSS)患者和44例健康对照(HC)CD 14单核细胞中I型干扰素(IFN)诱导基因上调(即所谓的“I型IFN特征”)的发生率,并将其与疾病表现和B细胞活化因子(BAFF)表达相关。使用真实的时间定量PCR在单核细胞中测量IFI 44 L、IFI 44、IFIT 3、LY 6 E和MX 1的表达。表达值用于计算每个受试者的I型IFN评分。然后比较I型IFN标记阳性的pSS患者(IFN评分≥10)和标记阴性的患者(IFN评分<10)的临床疾病表现和BAFF表达。使用单核细胞系进行生物测定以研究BAFF mRNA表达是否可由pSS患者血清中的I型IFN活性诱导。干扰素I型签名存在于55%的pSS患者中,相比之下,4.5%的HC。具有I型IFN特征的患者显示:(a)较高的EULAR干燥综合征疾病活动指数评分;较高的抗Ro 52、抗Ro 60和抗La自身抗体;较高的类风湿因子;较高的血清IgG;较低的C3、较低的绝对淋巴细胞和中性粒细胞计数;(B)较高的单核细胞BAFF基因表达。此外,签名阳性患者的血清诱导单核细胞中BAFF基因的表达。单核细胞IFN I型特征鉴定了具有较高临床疾病活动性以及较高BAFF mRNA表达的pSS患者亚组。这类患者可能受益于阻断IFN I型产生或活性的治疗。
To determine the prevalence of upregulation of interferon (IFN) type I inducible genes, the so called ‘IFN type I signature’, in CD14 monocytes in 69 patients with primary Sjögren's syndrome (pSS) and 44 healthy controls (HC) and correlate it with disease manifestations and expression of B cell activating factor (BAFF). Expression of IFI44L, IFI44, IFIT3, LY6E and MX1 was measured using real time quantitative PCR in monocytes. Expression values were used to calculate IFN type I scores for each subject. pSS patients positive for the IFN type I signature (IFN score≥10) and patients negative for the signature (IFN score<10) were then compared for clinical disease manifestations and BAFF expression. A bioassay using a monocytic cell line was performed to study whether BAFF mRNA expression was inducible by IFN type I activity in serum of patients with pSS. An IFN type I signature was present in 55% of patients with pSS compared with 4.5% of HC. Patients with the IFN type I signature showed: (a) higher EULAR Sjögren's Syndrome Disease Activity Index scores; higher anti-Ro52, anti-Ro60 and anti-La autoantibodies; higher rheumatoid factor; higher serum IgG; lower C3, lower absolute lymphocyte and neutrophil counts; (b)higher BAFF gene expression in monocytes. In addition, serum of signature-positive patients induced BAFF gene expression in monocytes. The monocyte IFN type I signature identifies a subgroup of patients with pSS with a higher clinical disease activity together with higher BAFF mRNA expression. Such patients might benefit from treatment blocking IFN type I production or activity.
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