Raupov R, Suspitsin E, Belozerov K, Gabrusskaya T, Kostik M. IFIH1 and DDX58 gene variants in pediatric rheumatic diseases. World J Clin Pediatr 2023; 12(3): 107-114 [PMID: 37342449 DOI: 10.5409/wjcp.v12.i3.107]
Corresponding Author of This Article
Mikhail Kostik, MD, PhD, Professor, Department of Pediatry, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Russia. kost-mikhail@yandex.ru
Research Domain of This Article
Rheumatology
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Pediatr. Jun 9, 2023; 12(3): 107-114 Published online Jun 9, 2023. doi: 10.5409/wjcp.v12.i3.107
IFIH1 and DDX58 gene variants in pediatric rheumatic diseases
Rinat Raupov, Evgeny Suspitsin, Konstantin Belozerov, Tatiana Gabrusskaya, Mikhail Kostik
Rinat Raupov, Konstantin Belozerov, Mikhail Kostik, Department of Pediatry, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
Evgeny Suspitsin, Department of Genetics, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
Tatiana Gabrusskaya, Department of Gastrointestinal Diseases, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
Author contributions: All authors contributed to the manuscript revision, read, and approved the submitted version.
Institutional review board statement: The Ethic Committee of Saint-Petersburg Sate Pediatric Medical University approved the study (protocol # 1/3 от 11.01.2021).
Informed consent statement: Written consent of legal representatives for inclusion of the data and using of the pictures was obtained.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mikhail Kostik, MD, PhD, Professor, Department of Pediatry, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Russia. kost-mikhail@yandex.ru
Received: December 30, 2022 Peer-review started: December 30, 2022 First decision: January 20, 2023 Revised: February 3, 2023 Accepted: April 24, 2023 Article in press: April 24, 2023 Published online: June 9, 2023
ARTICLE HIGHLIGHTS
Research background
The IFIH1 gene and the DDX58 gene both are involved in the interferon (IFN) type I signaling pathway. Monogenic diseases with the features of systemic rheumatic diseases were described in patients with these genetic variants. Rheumatic disease patients with IFN type I hyperactivation may have these variants.
Research motivation
Patients with rheumatic diseases with unusual manifestations (clinical features of interferonopathy) or resistant to standard treatment may have molecular variants in genes, regulating IFN I type pathway.
Research objectives
To describe children with different rheumatic diseases who have variants in DDX58 or IFIH1 genes.
Research methods
Clinical exome sequencing was performed 92 patients with different rheumatic diseases, and 14 children (10 girls and 4 boys) with DDX58 or IFIH1 genes were selected. They have the following diagnosis: Systemic autoinflammatory disease (n = 6), systemic lupus erythematosus (n = 5), juvenile dermatomyositis (n = 1), systemic onset juvenile idiopathic arthritis (n = 1), mixed connective tissue disease (n = 1). Real-time polymerase chain reaction with previous reverse transcription of RNA was used for IFN-I score assessment.
Research results
All patients had elevated IFN-I scores. Variants in both genes were described in the studied population.
Research conclusions
Patients with DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway. The RNA-based IFN-I score is a good tool to select candidates for further genetic analysis.
Research perspectives
Research perspectives are more on molecular tests in rheumatic diseases, more functional studies confirming the role of genetic variants, and an assessment of the efficacy and safety of drugs on new indications.
