Dataset Information

Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.

ABSTRACT:

Background

The familial clustering phenomenon together with environmental influences indicates the presence of a genetic and epigenetic predisposition to systematic lupus erythematosus (SLE). Interestingly, regarding lupus nephritis (LN), the worst complication of SLE, mortality, and morbidity were not consistent with SLE in relation to sexuality and ethnicity.

Summary

Genetic and epigenetic alterations in LN include genes and noncoding RNAs that are involved in antigen-presenting, complements, immune cell infiltration, interferon pathways, and so on. Once genetic or epigenetic change occurs alone or simultaneously, they will promote the formation of immune complexes with autoantibodies that target various autoantigens, which results in inflammatory cytokines and autoreactive immune cells colonizing renal tissues and contributing to LN.

Key messages

Making additional checks for immunopathology-related heredity and epigenetic factors may lead to a more holistic perspective of LN.

SUBMITTER: Mei X

PROVIDER: S-EPMC9386430 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Publications

Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.

Mei Xiaole X Jin Hui H Zhao Ming M Lu Qianjin Q

Kidney diseases (Basel, Switzerland) 20220609 4

<h4>Background</h4>The familial clustering phenomenon together with environmental influences indicates the presence of a genetic and epigenetic predisposition to systematic lupus erythematosus (SLE). Interestingly, regarding lupus nephritis (LN), the worst complication of SLE, mortality, and morbidity were not consistent with SLE in relation to sexuality and ethnicity.<h4>Summary</h4>Genetic and epigenetic alterations in LN include genes and noncoding RNAs that are involved in antigen-presenting ...[more]

PMID: 36157263

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Project description:BackgroundThere are currently no reliable diagnostic biomarkers or treatments for lupus nephritis (LN), a complication of systemic lupus erythematosus. Objective: We aimed to explore gene networks and potential biomarkers for LN by analyzing the GSE32591 and GSE113342 datasets from the Gene Expression Omnibus database, focusing on IRF8 and IRF8-related genes.MethodsWe used differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and the CIBERSORT algorithm for immune infiltration assessment. To validate the expression levels of the IRF8 gene in the kidneys of lupus mice models, we used quantitative real-time PCR (qRT-PCR) and Western blotting (WB). A diagnostic classifier was built using the RandomForest method to evaluate the diagnostic potential of selected key genes. To bridge our findings with potential therapeutic implications, we used the drug-gene interaction database to predict drugs targeting the identified genes.ResultsTwenty co-differentially expressed genes (DEGs) were identified, with IRF8 exhibiting significant expression differences and potential as a biomarker. Functional enrichment analysis revealed pathways associated with immune response. Validation through qRT-PCR and WB confirmed that the IRF8 gene and its protein exhibited elevated expression levels in the kidneys of lupus mice compared to control groups. The diagnostic classifier revealed impressive accuracy in differentiating LN from control samples, achieving a notable area under the curve values across various datasets. Additionally, immune infiltration analysis indicated significant differences in the immune cell profiles between the LN and control groups.ConclusionIRF8 and its related genes show promise as biomarkers and therapeutic targets for LN. These findings contribute to a deeper understanding of the molecular mechanisms involved in LN and may support the development of precision medicine strategies for improved patient outcomes.

Dataset Information

Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.

Background

Summary

Key messages

Publications

Association of Immune-Related Genetic and Epigenetic Alterations with Lupus Nephritis.

Similar Datasets

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