Immunogenic cell death-related key gene screening and validation in primary sjögren's syndrome
10.19405/j.cnki.issn1000–1492.2026.06.013
- VernacularTitle:原发性干燥综合征免疫原性细胞死亡关键基因筛选与验证
- Author:
Wanting HAO
1
;
Wenfeng WU
1
;
Lei HOU
2
;
Wukai MA
2
;
Peng YANG
2
Author Information
1. Department of Second Clinical Medical College， Guizhou University of Traditional Chinese Medicine， Guiyang 550003
2. Department of Rheumatology and Immunology， The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine， Guiyang 550003
- Publication Type:Journal Article
- Keywords:
primary Sjögren's syndrome;
immunogenic cell death;
immune cell infiltration;
CD8⁺ T cell subsets;
DDX58;
IFIH1;
CASP1;
IFNG
- From:
Acta Universitatis Medicinalis Anhui
2026;61(6):1075-1081
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo systematically screen and validate key immunogenic cell death （ICD）-related genes that play important roles in primary sjögren’s syndrome （pSS） using multi-omics data. MethodsGene expression profiles of pSS patients and healthy controls （GSE66795， 131pSS patients/29 healthy controls） were obtained from the Gene Expression Omnibus （GEO） database. Candidate genes were selected by intersecting these profiles with known ICD core gene sets and pSS-related targets. The CIBERSORT algorithm was used to analyze immune cell infiltration characteristics. Validation of gene expression was performed using transcriptomic data from sorted CD8⁺ T cell subsets （GSE93683）. Finally， labial gland tissues and peripheral blood samples from 10 pSS patients and 4 healthy controls were collected， and key genes were experimentally validated by reverse transcription quantitative polymerase chain reaction （RT-qPCR）. ResultsSeven intersecting genes from the ICD-differentially expressed genes （DEGs）-pSS intersection were identified ［caspase 1 （CASP1）， forkhead box P3 （FOXP3）， interferon-gamma （IFNG）， myeloid differentiation primary response 88 （MYD88）， toll-like receptor 7 （TLR7）， DExD/H-box helicase 58 （DDX58）， and interferon induced helicase C domain 1 （IFIH1）］. Immune infiltration analysis showed that in pSS labial gland tissues， the proportions of naïve B cells and dendritic cells significantly increased， while the proportions of resting NK cells and M0 macrophages decreased （P<0.05）. Transcriptomic data of CD8⁺T cell subsets indicated that IFIH1 expression was significantly elevated in central memory CD8⁺T cells （P<0.05）. RT-qPCR experimental validation revealed that DDX58， IFIH1， and CASP1 were significantly upregulated in both peripheral blood leukocytes and labial gland tissues of pSS patients （all P<0.05）， whereas IFNG expression increased in peripheral blood but decreased in labial gland tissues （P<0.05）. ConclusionThis study identified and confirmed DDX58， IFIH1， CASP1， and IFNG as key ICD-related genes in pSS through a combination of bioinformatics and experimental validation， providing new candidate targets for further understanding the immunopathological mechanisms of pSS.
