The objective of the study is to establish an in vitro model using iPSCs to test the hypotheses developed.
The primary objective is to generate, via the SAFE-IPS platform, 8 iPSC lines derived from blood samples taken from:
* Two patients with severe/diffuse SSc with multi-organ involvement (with anti-SCl-70 autoantibodies) * Two of their healthy close relatives * Two patients with uncomplicated SSc with localized involvement (with non-SCl-70 autoantibodies) * Two of their healthy close relatives
These 8 cell lines will be differentiated by several teams at the FHU REGENHAB into:
* Immune cells (monocytes/macrophages, neutrophils, dendritic cells, B/T lymphocytes) * Mesenchymal stromal cells * Myocardial cells * Skin cells (fibroblasts) * Synovial cells * Bronchial cells * Endothelial cells
This project aims to map cellular and tissue heterogeneity using iPSC lines obtained from patients with both severe and mild SSc, employing single-cell RNA-seq under various pathological conditions, with and without autologous (or even heterologous) autoimmune stimulation. For example, the percentages of different cell types comprising a tissue in these various situations will be calculated. Comparisons will be made with control groups using healthy iPSC lines by recruiting healthy subjects with the same genetic profile and gender as the patients.
Age between 18 and 85 years
Diagnosis of diffuse/severe systemic sclerosis by a physician for at least 12 months based on recommendations (according to ACR criteria)
Known positivity of autoimmunity directed against Scl-70
Diagnosis of systemic sclerosis by a physician for at least 12 months based on recommendations (according to ACR criteria)
Other diseases that may affect erythroid progenitor cells (non-exhaustive: active cancer, hematological malignancy, chemotherapy targeting DNA)
Patient in an exclusion period determined by another protocol
Protected populations according to French public health law (pregnant or breastfeeding women; individuals deprived of liberty by judicial or administrative decision; adults under legal protection (any form of guardianship))
Absence of informed consent