Fibrosis Lung, Fibrosis; Skin, Interstitial Lung Disease Due to Systemic Disease, Scleroderma, Systemic
Conditions
Brief summary
The main aim of the project is to identify key-factors involved in the development and progression of Systemic Sclerosis (SSc), a chronic invalidating rheumatic disease characterized by high mortality and insufficient treatment options. A cohort of patients with SSc will be collected at the Sahlgrenska University Hospital in Gothenburg, Skaraborg Hospital in Skövde, and Södra Älvsborg Hospital in Borås (Sweden). Thanks to a holistic approach including integrated analysis of blood, and skin samples as well as DNA, and with the use of state-of-the-art methods, this project aims to identify factors (e.g. genes, proteins, metabolites, and immune cell types) associated with the development of SSc and with the progression to a more aggressive phenotype. Functional studies using in vitro model systems and patient specimens will be also implemented. The findings of the current project could lead to the identification of possible diagnostic and prognostic markers for the disease as well as potential drug targets. This cohort will be also linked to the European Scleroderma Trial and Research (EUSTAR), which is an international SSc research network aiming to coordinate research activities on SSc from groups all over Europe in order to improve treatment, quality of life and mortality of patients with SSc.
Interventions
OTHERNo Intervention: Observational Cohort
no intervention
Sponsors
Sahlgrenska University Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Participants diagnosed with SSc according to the ACR and EULAR classification criteria
Exclusion criteria
* Diagnosis of Mixed connective tissue disease * Not speaking or reading Swedish * With severe cognitive impairment * With blood count below specified limits * Allergy to local anaesthetic (for subjects who will provide a skin biopsy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Predictors of disease activity and progression in plasma samples | The analyses will be performed in the entire study cohort at inclusion (including healthy subjects) and at the 2- and 5-year FU for patients with SSc. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Genetic markers of progression to an aggressive phenotype in subjects with SSc | Baseline DNA | 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. |
| Characterisation of skin cells in relation to SSc pathogenesis and progression | The analyses will be performed in the entire study cohort at inclusion (including healthy subjects) and at the 2- and 5-year FU for patients with SSc. | 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. |
| Memory B cell compartment and prognosis of SSc | Baseline PBMCs | 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. |
| PBMCs subsets and activation in the pathogenesis of SSc. | Baseline, 2- and 5- years FU | We aim to identify specific subsets of PBMCs associated with pathogenesis of SSc, especially T and B lymphocytes. |
| Assessment of Lung Function in Patients with Systemic Sclerosis through Impulse Oscillometry | Up to 2 years | Patients with systemic sclerosis will undergo impulse oscillometry. |
| Arthritis involvement in SSc. | Baseline, 2- and 5-years follow up | 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. |
| Assessment of Lung Function and Biomarker Profiling in Patients with Systemic Sclerosis through PExA sampling | Up to 2 years | Patients with systemic sclerosis from the WESST cohort will be invited to undergo PExA sampling. |
| Assessment of Lung Function in Patients with Systemic Sclerosis through Insert Gas Washout | Up to 2 years | Patients with systemic sclerosis will undergo insert gas washout. |
| Circulating fibrocytes and pathogenesis of SSc. | Baseline, 2- and 5- years FU | Here we aim to study circulating fibrocytes and to identify factors associated with downregulation of the transition of those cells into myofibroblasts. |
Countries
Sweden
Contacts
Primary ContactCristina Maglio, MD, PhD
Backup ContactYuan Zhang, MD, PhD
Outcome results
None listed