Objective

We investigated whether interferon (IFN) induced genes could serve as biomarkers for the detection of lymphoma development among patients with Sjögren's syndrome (SS).

Methods

Total RNA was extracted from 98 labial minor salivary glands (LMSG) biopsies of SS patients [61 not complicated by lymphoma (SS-nL) and 37 complicated by Non-Hodgkin Lymphoma (NHL) (SS-L)] and 67 matched peripheral blood (PB) samples, as well as from 30 LMSG biopsies and 17 matched PB derived from sicca controls (SC). RNA sequencing was performed in LMSG biopsies of high and low risk SS patients for lymphoma development and SC. Expression analysis of type I (MX-1, IFIT-1, IFI44 and ISG-15) and type II IFN induced (CXCL9/MIG-1, GBP-1) genes was performed by real time PCR.

Results

ISG-15 transcript levels were significantly higher in SS-L patients compared to SS-nL patients in both LMSG tissues and PB specimens. Additionally, MIG-1 was found to display higher expression values in LMSG tissues, but not in PB derived from SS-L patients compared to the SS-nL group. A coordinate expression in PB/LMSG of type I IFN (ISG-15, MX-1 and IFI44), but not type II IFN induced genes was also observed.

Conclusion

ISG-15 gene expression was able to distinguish SS-nL and SS-L at both periphery and tissue level and therefore could represent a novel biomarker for lymphoma development among SS patients. PB and LSMG seem to share a common transcriptional profile of type I IFN pathway.

中文翻译：

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干扰素 (IFN) 刺激的基因 15：干燥综合征淋巴瘤发展的新生物标志物

客观的

我们研究了干扰素 (IFN) 诱导的基因是否可以作为检测干燥综合征 (SS) 患者淋巴瘤发展的生物标志物。

方法

从 SS 患者的 98 例唇小唾液腺 (LMSG) 活检中提取总 RNA [61 例未并发淋巴瘤 (SS-nL) 和 37 例并发非霍奇金淋巴瘤 (NHL) (SS-L)] 和 67 例匹配的外周血(PB) 样本，以及来自 30 个 LMSG 活组织检查和 17 个来自干燥对照 (SC) 的匹配 PB。在淋巴瘤发展和 SC 的高风险和低风险 SS 患者的 LMSG 活检中进行 RNA 测序。通过实时PCR进行I型（MX-1、IFIT-1、IFI44和ISG-15）和II型干扰素诱导（CXCL9/MIG-1、GBP-1）基因的表达分析。

结果

在 LMSG 组织和 PB 标本中，SS-L 患者的 ISG-15 转录水平显着高于 SS-nL 患者。此外，与 SS-nL 组相比，发现 MIG-1 在 LMSG 组织中显示更高的表达值，但在源自 SS-L 患者的 PB 中没有。还观察到 I 型干扰素（ISG-15、MX-1 和 IFI44）在 PB/LMSG 中的协调表达，但没有观察到 II 型干扰素诱导基因。

结论

ISG-15 基因表达能够在外周和组织水平区分 SS-nL 和 SS-L，因此可以代表 SS 患者淋巴瘤发展的新生物标志物。PB 和 LSMG 似乎共享 I 型 IFN 途径的共同转录谱。