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

Ilir I Cinoku; Kleio-Maria Verrou; Evangelia Piperi; Michael Voulgarelis; Haralampos M Moutsopoulos; Clio P Mavragani

doi:10.1016/j.jaut.2021.102704

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

J Autoimmun. 2021 Sep:123:102704. doi: 10.1016/j.jaut.2021.102704. Epub 2021 Jul 20.

Authors

Ilir I Cinoku¹, Kleio-Maria Verrou², Evangelia Piperi³, Michael Voulgarelis⁴, Haralampos M Moutsopoulos⁵, Clio P Mavragani⁶

Affiliations

¹ Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Supported by a competitive scholarship from the Academy of Athens, Greece.
² Center of New Biotechnologies & Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
³ Department of Oral Medicine and Pathology, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece.
⁴ Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
⁵ Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Academy of Athens, Athens, Greece.
⁶ Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Supported by a competitive scholarship from the Academy of Athens, Greece; Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Joint Academic Rheumatology Program, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: kmauragan@med.uoa.gr.

PMID: 34298409
DOI: 10.1016/j.jaut.2021.102704

Abstract

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.

Keywords: Biomarker; Interferon; Interferon-related genes; Lymphoma; Sjogren's syndrome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Biomarkers
Cytokines / genetics*
Female
Humans
Interferon Type I / physiology
Lymphoma / diagnosis*
Male
Middle Aged
RNA, Messenger / analysis
Sjogren's Syndrome / complications*
Sjogren's Syndrome / immunology
Sjogren's Syndrome / pathology
Ubiquitins / genetics*

Substances

Biomarkers
Cytokines
Interferon Type I
RNA, Messenger
Ubiquitins
ISG15 protein, human