Innate Immunity in Cutaneous Lupus Erythematosus

Abstract

BackgroundCutaneous Lupus Erythematosus (CLE) is an autoimmune skin disorder. The adaptive immune system is involved in the etiology of CLE. CLE lesions respond to inhibition of endosomal toll like receptors, hence supporting other disease mechanisms in its pathogenesis.HypothesisGenes associated with defects in the innate immune system would be differentially expressed in CLE skin compared to normal controls.MethodUsing the Gene Expression Omnibus, gene expression data from skin biopsies of patients with cutaneous and normal controls were compared. Data sets selected included: GSE109248, GSE81071, GSE52417, and GSE95474, including acute lupus, subacute lupus, discoid lupus, and normal skin samples. GEO2R was used to analyze the gene expressions between the two sample groups for each data set. STRING (Search Tool for the Retrieval of Interacting Genes/Proteins), GeneCard, and KEGG (Kyoto Encyclopedia of Genes and Genomes Pathway) analysis were used to identify the interaction and function of specific genes.ResultsGenes associated with the NOD like receptor (NLR) signaling pathway were consistently differentially expressed in discoid lupus skin samples in all data sets (p‐value < 8.74e‐05). Five genes associated with the NLR signaling pathway were found to be upregulated in skin samples of discoid lupus patients in all datasets compared to normal controls. These included: STAT1 (signal transducer and activator of transcription 1), Oligoadenylate Synthetases (OAS1, OAS2, OAS3), and AIM2 (absent in melanoma 2). These five genes are known to be involved with transcription activation, regulation of viral infection, and interferon response.ConclusionGenes associated with the NLR signaling pathway are differentially expressed in the skin lesions of lupus patients, specifically discoid lupus, compared to normal controls, supporting the role of the innate immune system in its pathogenesis. Further validation studies using experimental methods such as polymerase chain reaction are needed.