Autoimmunity

Statement of the Problem: Systemic sclerosis (SSc) is an autoimmune rheumatic disease characterized by vasculopathy, inflammation and fi brosis. It is a complex and heterogeneous disease, as many organs of the body may be aff ected and symptoms vary among individuals. As the aetiology and pathogenesis of the disease are currently unclear, its prognosis and diagnosis are challenging and thus up to date there is no cure for SSc. Th erefore, the purpose of this study is to discover specific proteomic biomarkers gaining insights into the mechanisms implicated in SSc pathogenesis and facilitating the early prognosis, more accurate diagnosis and therapeutic targeting of the disease.

 

Methodology & Th eoretical Orientation: Human biopsies were obtained from aff ected and non-aff ected skin areas of SSc patients and have been classifi ed based on histological criteria. Proteins were extracted from human skin biopsies, purified, reduced, alkylated and digested with trypsin. Purified peptides were analyzed on a Waters SYNAPT G2Si HDMS instrument operated in ion mobility mode using a UDMSE approach. Data were processed by the Progenesis QI and functional annotation analysis performed using multiple bioinformatics resources.

 

Findings: Proteomic analysis led to identifi cation and quantifi cation of more than 1500 diff erentially expressed proteins.Differential expression of approximately 1000 out of these proteins including interferons and interleukins, have statistically significant fold Change of ≥1.5 or ≤0.667. Further pathway analyses showed that the identifi ed dysregulated proteins were involved in multiple pathways including, antigen processing and presentation and complement pathway, which is known to be associated with autoimmune diseases.

 

Conclusion & Significance: Using MS-based proteomic analyses of SSc human skin biopsies, we identifi ed several proteins that might be implicated in the pathogenesis and development of SSc. Th e most diff erentially expressed proteins as well as differentially expressed proteins that are involved in autoimmunity-related pathways could be considered as potential SSc biomarkers.

 

This work has received support from the EU/EFPIA/ Innovative Medicines Initiative Joint Undertaking PRECISESADS grant

no 115565.www.precisesads.eu