The Upregulation of Inflammasome Genes and Modulators is Associated with Disease Activity in Chronic Cutaneous Lupus

Abstract

Introduction Chronic lupus erythematosus, commonly discoid lupus, is an autoimmune skin disorder characterized by waxing and waning disease activity that can lead to scarring and disfigurement. Genes associated with inflammasome activation has been associated with systemic lupus erythematous, which has similar pathogenetic mechanisms. Methods Datasets selected from the Gene Expression Omnibus (GEO), GSE120809 and GSE119207, were used to compare gene expression between lesional and non-lesional samples (skin and hair follicle) from discoid lupus patients. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, Gene Card, and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis were used to identify the interaction and function of specific genes. Results There were a total of 14 discoid lesional samples, 17 discoid non-lesional samples, and 4 normal controls. Genes associated with the activation and modulation of the inflammasome, signal transducer and activator of transcription 1 (STAT1), oligoadenylate synthase (OAS2, OAS3), and absent in melanoma 2 (AIM2), were found to be upregulated in lesional (n=7) versus non-lesional discoid lupus skin (n=10) (adjusted p-value < 0.01). STAT1, OAS1, OAS2, and OAS3, were likewise upregulated in lesional discoid hair follicle (n=7) versus non-lesional discoid hair follicle skin (n=7) (adjusted p-value < 0.009). Similar results as above were obtained when comparing lesional hair follicle versus normal hair follicle (n=4). These genes are associated with interferon response and transcription activation. Conclusion Genes associated with activation and modulation of the inflammasome are upregulated in the active skin lesions and hair follicle of discoid lupus patients compared to non-lesional skin, hair follicle, and normal controls, supporting its role in discoid lupus disease activity. Validation studies using standardized cutaneous activity metrics and further experimental methods are needed.