Western Sweden Systemic Sclerosis Project

Here we will analyse plasma circulating molecules (including but not limited to metabolites, cytokines, lipids, proteins, antibodies, exosomes etc) to identify factors involved in the pathogenesis of SSc by comparing those factors in plasma from subjects with SSc vs. healthy subjects. We also aim to identify factors involved in the prognosis of SSc by comparing circulating molecules in plasma from subjects with limited form SSc vs. diffuse form SSc. We plan to screen plasma samples from study participants for molecules that can be relevant for the pathogenesis and the prognosis of SSc.

all DNA samples from our cohort will be subjects to either next generation sequencing or GWAS as well as epigenetic studies. Single nucleotide polymorphisms of interest will also analysed in these specimens. Data will be analysed independently and/or merged with those of other large cohorts from all over Europe to identify genetic factors associated with the development of SSc as well as the prognosis and the response to treatment.

Here we will study skin cells involved in the fibrotic processes in the skin, i.e. fibroblasts and keratinocytes, as well as skin immune cells. We aim to define factors that trigger the fibroblasts to switch to a pro-fibrotic phenotype and factors associated with the progression of the skin disease. Fibroblasts, keratinocytes and immune cells will be isolated and cultured from skin biopsies. Metabolomics, lipidomics, and proteomics will be performed on cell extracts. We will also perform functional studies. Single-cell RNA-Seq in skin biopsies will be performed.

The overall aim of this WP is to identify how the memory B cell compartment (CD27dull and/or CD27bright memory B cells) are modulated in patients in the initial phase of SSc, therefore only subjects with onset of Raynaud's phenomenon <5 years will be included, plus up 6 controls. We will determine this by flow cytometry and by immunoglobulin sequencing as well as RNA sequencing in patients during the initial phase of the disease with the goal to find prognostic markers during early disease.

We aim to identify specific subsets of PBMCs associated with pathogenesis of SSc, especially T and B lymphocytes.

Here we aim to study circulating fibrocytes and to identify factors associated with downregulation of the transition of those cells into myofibroblasts.

The aim of this work package is to assess the burden of articular manifestations in systemic sclerosis (SSc) and to develop a validated articular score.

Patients with systemic sclerosis from the WESST cohort will be invited to undergo PExA sampling.

Patients with systemic sclerosis will undergo insert gas washout.

Patients with systemic sclerosis will undergo impulse oscillometry.