Shared inflammatory and skin-specific gene signatures reveal common drivers of discoid lupus erythematosus in canines, humans and mice

Using Gene Expression Analysis to Understand Complex Autoimmune Skin Disease Patients: A Series of Four Canine Cutaneous Lupus Erythematosus Cases

“…Comparative analysis of canine CLE cases with human and mouse CLE revealed significant overlapping genes, supporting the conservation of inflammatory signatures across species. We previously published a similar frequency of DEG overlap in discoid lupus, which shares many DEGs with the complex CLE cases presented here (18). Of note, the clinical and histopathological features observed in CLE case 3 led us to consider the mucocutaneous variant of chronic CLE, as the dog experienced recurrent mucoulcerative lesions and a pattern of interface dermatitis mostly involving the hair follicles, similar to what has been previously observed in reported CLE cases (55).…”

“…We chose NanoString technology to analyze RNA from these FFPE samples because the technology works well for fragmented RNA and avoids amplification, which could introduce a data acquisition bias ( 29 ). To ascertain whether the cases presented here aligned with cases with confirmed diagnoses, we performed hierarchical clustering using ClustVis with GSE160260 [canine DLE; dataset originally published in Garelli et al ( 18 )] and GSE171079 [canine pemphigus including pemphigus erythematosus; dataset originally published in Raef et al ( 20 )]. Hierarchical clustering of gene expression for the whole panel differentiates between healthy controls and all cases, with a significant overlap between DLE and the cases presented here ( Supplementary Figures 1A,B ).…”

“…The 160 custom canine gene dataset presented here (GSE180276), 755 genes murine cancer immune dataset by Mande et al ( 22 ), and GSE95474 dataset ( 23 ) were compared. Common denominator genes were identified in Excel using the formula “=IF(ISERROR(VLOOKUP(A2,$B$2:$B$1001,1,FALSE)),FALSE, TRUE).” Alternate gene names for values that were retrieved as FALSE were queried using GeneCards.org, and naming conventions were matched across all species, which resulted in 160 overlapping genes for canine vs. human (entire canine codeset), and 92 genes overlapping all three species [see also ( 18 )].…”

“…RNA was isolated from 30 µm tissue curls using the Qiagen formalin-fixed paraffin-embedded (FFPE) tissue RNeasy kit per the manufacturer's directions and as previously described (18)(19)(20). RNA was quantified using a NanoDrop spectrophotometer.…”

“…The “One Health Approach,” which is a collaborative, multisectoral, and transdisciplinary school of thought, recognizes the interconnection between the health of people and animals and their shared environment and emphasizes the need to combine investigative methods and animal models for studying human diseases ( 17 ). We (Garelli et al) recently performed a comparative transcriptomics study of canine and human discoid lupus erythematosus (DLE) and found conserved gene expression patterns ( 18 ). The objective of this study was to determine if we can diagnose unclear CLE cases using gene expression profiling.…”