RNASEQ ANALYSIS OF THE IMMUNOLOGICAL DISTURBANCES IN PYODERMA GANGRENOSUM
- Gabriel J. Tobón, Colombia
Abstract
Background and Aims
Pyoderma gangrenosum (PG) is an inflammatory disease, which is histologically characterized by an inflammatory infiltrate mediated mainly by granulocytes without evidence of infection. The pathophysiology of this disease is not clear, primarily the uncontrolled production of pro-inflammatory cytokines, which activate neutrophils are the reason why PG is classified as auto-inflammatory. To evaluate the immune profile of the disease, we conducted an RNAseq analysis in skin biopsies of four patients with PG and four healthy controls.
Methods
After total RNA extraction, mRNA was obtained by an Oligo-dT sequence. Afterwards sequenced in an Illumina platform, the readings were mapped against the GRCh38 genome.
Results
We obtained information of 19799 genes, 2798 genes were up-regulated and 2842 down-regulated comparing PG vs. healthy skin. The primary 100 genes were selected in each group. After a functional enrichment analysis, the central up-regulated genes were lytic tissue-destroying genes such as MMPs but also wound healing and angiogenesis genes. Also, pro-inflammatory proteins and neutrophil chemokines, reported in the literature associated with PG, were identified. Besides, an exciting group of genes, S100A genes, were remarkably up-regulated, whose functions of regulating the immune response could trigger the excessive degranulation of neutrophils that damages tissue. Finally, we observed the down-regulation of skin structural support and permeability genes as KRT2 and CLDN10 and the low expression of epidermal growth factors such as ERBB4.
Conclusions
The homeostasis impairment of these molecules in the skin can trigger a PG-type lesion; these findings will be functionally validated in vitro and animal models.