Interferon (IFN)-stimulated gene 15: A novel biomarker for lymphoma development in Sjögren's syndrome

• Published in: Journal of autoimmunity 2021-09, Vol.123, p.102704-102704, Article 102704
• Main Authors: Cinoku, Ilir I., Verrou, Kleio-Maria, Piperi, Evangelia, Voulgarelis, Michael, Moutsopoulos, Haralampos M., Mavragani, Clio P.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biomarker; Biomarkers; Cytokines - genetics; Female; Humans; Interferon; Interferon Type I - physiology; Interferon-related genes; Lymphoma; Lymphoma - diagnosis; Male; Middle Aged; RNA, Messenger - analysis; Sjogren's syndrome; Sjogren's Syndrome - complications; Sjogren's Syndrome - immunology; Sjogren's Syndrome - pathology; Ubiquitins - genetics
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2021.102704

We investigated whether interferon (IFN) induced genes could serve as biomarkers for the detection of lymphoma development among patients with Sjögren's syndrome (SS). 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. 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. 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. •Activation of type I and II IFN pathways are involved in SS pathogenesis.•ISG-15 could serve as a novel biomarker for SS related lymphoma development.•SS PB and LSGB share a common type I IFN related transcriptional profile.