Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis.
Type I and II interferon signatures in Sjogren's syndrome pathogenesis: Contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis.
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DOI：
10.1016/j.jaut.2015.07.002
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发表时间：
2015-09
影响因子：
12.8
通讯作者：
Mavragani CP
中科院分区：
文献类型：
--
作者：
Nezos A;Gravani F;Tassidou A;Kapsogeorgou EK;Voulgarelis M;Koutsilieris M;Crow MK;Mavragani CP
I 型和 II 型干扰素 (IFN) 均与干燥综合征 (SS) 的发病机制有关。我们的目的是探讨 I 型和 II 型 IFN 特征在不同 SS 临床表型（包括淋巴瘤发展）产生中的贡献。对 SS 患者 (n=31)、SS 并发淋巴瘤患者 (n=13) 和健康对照 (HC, n=30) 的外周血 (PB) 进行实时 PCR，检测 I 型 IFN 优先诱导的 3 个干扰素诱导基因 (IFIG)、IFNγ 优先诱导的 2 个 IFIG 以及 IFNα 和 IFNγ 基因。对来自 31 名 SS 患者、10 名 SS 淋巴瘤患者和 17 名干燥对照 (SC) 的小唾液腺组织 (MSG) 进行了相同的分析。在 PB 和 MSG 组织中，与 HC 和 SC 患者相比，SS 患者分别观察到 I 型和 II 型 IFIG 过度表达，其中 PB 中以 I 型 IFN 特征为主，MSG 组织中以 II 型 IFN 特征为主。在 SS 淋巴瘤 MSG 组织中，与 SS 和 SC 相比，观察到较低的 IFNα，但较高的 IFNγ 和 II 型 IFIG 转录物。在接受者操作特征曲线分析中，MSG 组织中的 IFNγ/IFNα mRNA 比率显示出对淋巴瘤发展的最佳辨别力。 I 型和 II 型 IFN 特征的离散表达模式可能与不同的 SS 临床表型有关。此外，诊断性唾液腺活检中的 IFNγ/IFNα mRNA 比率被提议作为一种新的组织病理学生物标志物，用于预测 SS 背景下原位淋巴瘤的发展。
Both type I and II interferons (IFNs) have been implicated in the pathogenesis of Sjogren's syndrome (SS). We aimed to explore the contribution of type I and II IFN signatures in the generation of distinct SS clinical phenotypes including lymphoma development. Peripheral blood (PB) from SS patients (n=31), SS patients complicated by lymphoma (n=13) and healthy controls (HC, n=30) were subjected to real-time PCR for 3 interferon inducible genes (IFIGs) preferentially induced by type I IFN, 2 IFIGs preferentially induced by IFNγ as well as for IFNα and IFNγ genes. The same analysis was performed in minor salivary gland tissues (MSG) derived from 31 SS patients, 10 SS-lymphoma patients and 17 sicca controls (SC). In PB and MSG tissues, overexpression of both type I and type II IFIGs was observed in SS patients versus HC and SC, respectively, with a predominance of type I IFN signature in PB and a type II IFN signature in MSG tissues. In SS-lymphoma MSG tissues, lower IFNα, but higher IFNγ and type II IFIG transcripts compared to both SS and SC were observed. In receiver operating characteristic curve analysis, IFNγ/IFNα mRNA ratio in MSG tissues showed the best discrimination for lymphoma development. Discrete expression patterns of type I and II IFN signatures might be related to distinct SS clinical phenotypes. Additionally, IFNγ/IFNα mRNA ratio in diagnostic salivary gland biopsies is proposed as a novel histopathological biomarker for the prediction of in situ lymphoma development in the setting of SS.