Bibliographic Details
| Title: |
IFN-I Score and Rare Genetic Variants in Children with Systemic Lupus Erythematosus |
| Authors: |
Rinat K. Raupov, Evgeny N. Suspitsin, Elvira M. Kalashnikova, Lubov S. Sorokina, Tatiana E. Burtseva, Vera M. Argunova, Rimma S. Mulkidzhan, Anastasia V. Tumakova, Mikhail M. Kostik |
| Source: |
Biomedicines, Vol 12, Iss 6, p 1244 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
childhood-onset systemic lupus erythematosus, IFN-I score, SLE-associated genes, PTPN22, TREX1, Biology (General), QH301-705.5 |
| More Details: |
Introduction: Interferon I (IFN I) signaling hyperactivation is considered one of the most important pathogenetic mechanisms in systemic lupus erythematosus (SLE). Early manifestation and more severe SLE courses in children suggest a stronger genetic influence in childhood-onset SLE (cSLE). Aim: To evaluate IFN-I score and SLE-associated genetic variants in cSLE. Material and Methods: 80 patients with cSLE were included in the study. IFN I-score was assessed by real-time PCR quantitation of 5 IFN I-regulated transcripts (IFI44L, IFI44, IFIT3, LY6E, MXA1) in 60 patients. Clinical exome sequencing (CES) was performed in 51 patients. Whole-exome sequencing was performed in 32 patients with negative results of CES. Results: 46/60 patients (77%) had elevated IFN-I scores. Leucopenia and skin involvement were associated with over-expression of IFI44 and IFI44L, while hypocomplementemia—with hyperactivation of IFIT3, LY6E, and MX1. No correlation of IFN-I score with disease activity was found. At least one rare genetic variant, potentially associated with SLE, was found in 29 (56.9%) patients. The frequency of any SLE-genetic variants in patients with increased IFN scores was 84%, in patients with normal IFN scores—33%, and in the group whose IFN score was not assessed was 65% (p = 0.040). The majority of genetic variants (74%) are functionally related to nucleic acid sensing and IFN-signaling. The highest frequency of genetic variants was observed in Sakha patients (9/14; 64.3%); three and two unrelated patients had identical variants in PTPN22 and TREX1 genes, respectively. Conclusions: More than half of patients with childhood-onset SLE have rare variants in SLE-associated genes. The IFN-I score could be considered a tool for the selection of patients for further genetic assessment in whom monogenic lupus is suspected. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2227-9059 |
| Relation: |
https://www.mdpi.com/2227-9059/12/6/1244; https://doaj.org/toc/2227-9059 |
| DOI: |
10.3390/biomedicines12061244 |
| Access URL: |
https://doaj.org/article/4e8d648124e74cdba2465be24f105635 |
| Accession Number: |
edsdoj.4e8d648124e74cdba2465be24f105635 |
| Database: |
Directory of Open Access Journals |
