Background/Purpose: Vasculitis encompasses multiple conditions united by end-organ damage due to an immune-mediated reaction against the vasculature. Leukocytoclastic vasculitis (LCV) is a subtype of cutaneous vasculitis with considerable heterogeneity in etiology, duration, prognosis, and treatment. The pathophysiology underlying LCV remains poorly characterized and targeted treatments are limited.

Methods: 43 skin biopsies with confirmed LCV on histopathology and 5 skin biopsies from healthy controls underwent bulk RNA sequencing. Medical records were reviewed to determine an underlying etiology of LCV, when possible. Differential gene expression analysis and unsupervised hierarchical clustering were performed using DESeq2. Differentially expressed genes were identified with FDR < 0.5, padj ≤ 0.05, and log2FoldChange ≥ 0.5 (upregulated) or ≤ -0.5 (downregulated). Gene ontology enrichment analysis was performed using clusterProfiler. Etiologies with three or more samples were included in comparative analysis. This study was completed under University of Michigan Medical School IRB HUM00261031.

Results: Age at the time of biopsy ranged from 5-85 years old. Etiologies of LCV were unknown (33%), infection (26%), rheumatologic (21%), medications (14%), paraneoplastic (4.7%), and inflammatory bowel disease (IBD) (2.3%). Principal component analysis showed considerable heterogeneity between LCV samples. 2,246 genes are differentially expressed between all LCV samples and controls (915 upregulated, 1,331 downregulated). Genes upregulated in LCV were enriched for GO biological processes, including leukocyte migration, chemotaxis, and leukocyte cell-cell adhesion. 301 upregulated genes were shared in all LCV etiologies (unknown, infection, rheumatologic, medications) and were enriched for GO biological process of chemotaxis, leukocyte migration, and leukocyte cell-cell adhesion.

Conclusion: Analysis of LCV samples revealed shared upregulation of GO biologic processes related to leukocyte adhesion. Pharmacologic targeting of this pathway may serve as a potential therapeutic treatment for this subtype of vasculitis. Limitations of this study include small sample size and variable availability of associated clinical information. Future work with a larger sample size may validate these findings.

Table 1. Patient characteristics

Figure 1. PCA plot of bulk RNA-sequencing data stratified by LCV etiology

Figure 2. GO biologic process enrichment of 301 common upregulated genes

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/bulk-rna-sequencing-of-leukocytoclastic-vasculitis-skin-biopsies-show-upregulation-of-leukocyte-migration-genes/