Systemic Sclerosis, Inflammatory Myopathies
Conditions
Keywords
Scleroderma, Myopathy, Multi-OMICS, Biomarkers, Single-cell
Brief summary
Systemic sclerosis and inflammatory myopathies, which sometimes combine (scleromyositis), have shared pathophysiological elements. In both diseases, many cell subtypes are involved in damage to organs such as T lymphocytes, B lymphocytes, and unconventional (non-B, non-T) lymphocytes called innate lymphoid cell (ILC). The increasing complexity of our understanding of the immune system (multiplication of recognized cell subtypes) also makes the strategies for analyzing pathophysiological mechanisms more complex. Currently, no biomarker perfectly predicts the phenotype and evolution of patients. Multi-OMIC analyzes will be performed (identification of cell populations as well as genomic, transcriptomic and proteomic characterization) in blood and tissue samples (skin and muscle biopsy) in patients with systemic sclerosis and inflammatory myopathies, with the objective of identifying discriminating molecular signatures (biomarkers) according to the characteristics of the disease and its evolution.
Detailed description
Cohort study, monocentric, comparative, non-randomized, open-label, prospective and longitudinal, quasi-experimental. Participating subjects will be classified according to their clinical, biological and additional investigations into one of the 4 populations presented in the eligibility criteria. A 1st sampling point will be carried out at inclusion visit (baseline). Prospective follow-up of participating patients will be carried out as part of their routine care (1 to 2 visits per year or more if disease complications appear). During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the disease. During the follow-up, 2 more sampling points will be carried out (blood and / or skin) on each participating patient. Blood samples and muscle biopsies will be carried out in the usual way during diagnostic and therapeutic management. An additional volume of blood, an additional muscle biopsy (on the occasion of the one performed for diagnosis) and two superficial skin biopsies (1 sclerotic tissue & 1 healthy tissue) will be taken for research purposes. Inclusion in this cohort will not change the management of the patient, either with regard to his treatment or his follow-up. Multi-omics analyzes will include single cell RNAseq, as well as proteomics and genomics analysis: * Transcriptomic analysis will be performed on PMBC, muscle and skin. * Genomic analysis (exome & whole genome) will be performed on PMBC, muscle and skin. * Proteomic analysis will be performed on serum, PMBC, muscle and skin. * Single cell analysis will be performed on PMBC, muscle and skin. During the analysis, the clinical characteristics of baseline, the treatments and the evolutions during the follow-up will be compared to reveal the clinical relevance of the multi-OMIC signatures.
Interventions
Skin, muscle fiber and blood sampling
Sponsors
University Hospital, Strasbourg, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Control population without inflammatory myopathy (population 1), suspected myopathy for whom a blood test and muscle biopsy are required to confirm the diagnosis * Confirmed inflammatory myopathy (population 2) * Control population without systemic sclerosis (population 3), with primary Raynaud's phenomenon * Early diffuse systemic cutaneous scleroderma (population 4) * Male or female (age ≥ 18, no upper age limit)
Exclusion criteria
Populations 1 & 2 * Contraindication to muscle biopsy * Diagnosed for another neuromuscular disease * Taking an immunosuppressant / immunomodulator treatment within 3 months before inclusion * Unbalanced cardiovascular pathology Population 3 & 4 * Contraindication to skin biopsy * Capillaroscopic and / or immunological anomaly suggesting scleroderma * Suspicion of scleroderma but diagnosed for another connectivitis * Immunosuppressive treatment (corticosteroids\> 15 mg, methotrexate, mycophenolate mofetil) introduced for more than 1 month * Active or recent cancer \<3 years (apart from non-melanoma skin cancer). For all \- Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at one year and versus disease early stage. | At 12 months | Comparison of the molecular profiles (i.e., genomic \[New Generation Sequencing\], transcriptomic \[RNA chip\], proteomic \[mass spectrometry\] and identification of cell population \[single cell RNA sequencing\] between systemic sclerosis and inflammatory myopathies at one year and versus disease early stage. |
| Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of systemic sclerosis during 5 years. | At Day 1 | This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology. During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the systemic sclerosis. |
| Evolution of the molecular profiles (i.e., genomic [New Generation Sequencing], transcriptomic [RNA chip], proteomic [mass spectrometry] and identification of cell population [single cell RNA sequencing]) of inflammatory myopathies during 5 years. | At Day 1 | This study is descriptive (non-analytical), without prior hypothesis. Molecular profiles will be assessed by integration of multi-OMIC tools from a wide range of areas of biochemistry, chemistry, physics, computing science and molecular biology. During the 5-year follow-up, the investigating physician will remain attentive to the appearance of a new clinical element which will mark the course of the inflammatory myopathies. |
| Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at 5 years and versus disease early stage. | At 5 years | Comparison of the molecular profiles (i.e., genomic \[New Generation Sequencing\], transcriptomic \[RNA chip\], proteomic \[mass spectrometry\] and identification of cell population \[single cell RNA sequencing\] between systemic sclerosis and inflammatory myopathies at 5 years and versus disease early stage. |
| Comparison of the molecular profiles between systemic sclerosis and inflammatory myopathies at disease early stage. | Day 1 | Comparison of the molecular profiles (i.e., genomic \[New Generation Sequencing\], transcriptomic \[RNA chip\], proteomic \[mass spectrometry\] and identification of cell population \[single cell RNA sequencing\] between systemic sclerosis and inflammatory myopathies at disease early stage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Identification of molecular profiles specific to the impact of the implementation of targeted treatments in systemic sclerosis and inflammatory myopathies | 5 years | Study of the molecular profile (i.e., genomic \[New Generation Sequencing\], transcriptomic \[RNA chip\], proteomic \[mass spectrometry\] and identification of cell population \[single cell RNA sequencing\]) of systemic sclerosis before and after the implementation of targeted treatments (immunomodulators, cell therapies). |
| Assessment of the presence of discriminating molecular profiles in different tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies | 5 years | Compare the molecular profiles of blood (serum, PMBC), skin (sclerotic, healthy) and muscle, of early and advanced systemic sclerosis and inflammatory myopathies |
| Assessment of the presence of discriminating molecular profiles in different cell subpopulations within these tissues (blood, skin, muscle) in systemic sclerosis and inflammatory myopathies | 5 years | Compare the molecular profiles in different cell subpopulations within blood, skin and muscle tissues by single cell analysis in systemic sclerosis and inflammatory myopathies |
| Identification of molecular profiles specific to the evolution of clinical and biological characteristics of systemic sclerosis and inflammatory myopathies | 5 years | Study of the molecular profile (i.e., genomic \[New Generation Sequencing\], transcriptomic \[RNA chip\], proteomic \[mass spectrometry\] and identification of cell population \[single cell RNA sequencing\]) of systemic sclerosis during a systemic or infectious complication (initial profile compared to the profile at the time of the complication) |
Countries
France
Contacts
Primary ContactAlain MEYER, MD
Outcome results
None listed