Background/Purpose: Eosinophilic fasciitis (EF) is a rare scleroderma-like disorder with less than 200 cases reported. Due to the rarity of the disease, data regarding its pathophysiology are lacking. Herein we aimed at studying the transcriptome and the proteome of EF fibroblasts.

Methods: Skin fibroblasts from EF patients (n=4), systemic sclerosis (SSc) patients (n=4), and healthy controls (HC) (n=4), were cultured and harvested for transcriptomic and proteomic analysis. Analyses were performed using next generation sequencing and label-free quantification, respectfully. Functional analyses were performed using Ingenuity Pathway Analysis and Panther softwares.

Results: Five hundred and nine genes involved in 14 biological processes (BP) and 199 pathways were differentially expressed between EF and control groups. Among them, the circadian clock system (CCS) (p=1.70 10^-9), the plasminogen-activating cascade (PAC) (p=3.82 10^-5), the FGF signalling pathway (p=1.15 10^-4), and the integrin signalling pathway (p=1.33 10^-3) were overrepresented. When comparing EF to HC genes, Panther showed overrepresented down-regulated pathway including CCS (p=1.71 10^-12), and overrepresented up-regulated pathways such as flavin biosynthesis, (p=9.22 10^-4), PAC (p=1.19 10^-6), de novo purine biosynthesis (p=1.63 10^-3), FGF signalling pathway (p=1.47 10^-3) and integrin signalling pathway (p=9.14 10^-4). When comparing EF to SSc genes Panther showed overrepresented down-regulated CCS (p=2.51 10^-4).

Two hundred and twenty four proteins involved in 10 BP and 126 pathways were differentially expressed between EF and control groups. When comparing EF to HC proteins, Panther showed specific overrepresented up-regulated biological processes such as vesicle-mediated transport (p=4.66 10^-5) and intracellular protein transport (p=1.24 10^-4), and overrepresented up-regulated pathways such as 5-hydroxytryptamine degradation (5-HTD) (p=1.56 10^-4) and overrepresented down-regulated pathways such as heterotrimeric G-protein signalling pathways-rod outer segment photo-transduction (HTGSP) (p=1.24 10^-4). When comparing EF to SSc proteins, Panther showed specific overrepresented down-regulated biological processes such as 5-HTD (p=4.48 10^-4), and overrepresented down-regulated pathways such as HTGSP (p=1.98 10^-4), and ubiquitin proteasome pathway (p =1.05 10^-3).

Conclusion: This work described the transcriptome and the proteome of EF fibroblasts and highlighted significant specificities of EF fibroblasts when compared to HC and SSc.

« Back to ACR/ARP Annual Meeting 2019

ACR Meeting Abstracts - https://acrabstracts.org/abstract/proteomic-and-transcriptomic-analysis-of-human-eosinophilic-fasciitis-fibroblasts/