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Abstract We aimed to develop a systemic sclerosis (SSc) subtypes classifier tool to be used at the patient’s bedside. We compared the heart rate variability (HRV) at rest (5-min) and in response to orthostatism (5-min) of patients (n = 58) having diffuse (n = 16, dcSSc) and limited (n = 38, lcSSc) cutaneous forms. The HRV was evaluated from the beat-to-beat RR intervals in time-, frequency-, and nonlinear-domains. The dcSSc group differed from the lcSSc group mainly by a higher heart rate (HR) and a lower HRV, in decubitus and orthostatism conditions. Stand-up maneuver lowered HR standard deviation (sd_HR), the major axis length of the fitted ellipse of Poincaré plot of RR intervals (SD2), and the correlation dimension (CorDim) in the dcSSc group while increased these HRV indexes in the lcSSc group (p = 0.004, p = 0.002, and p = 0.004, respectively). We identified the 5 most informative and discriminant HRV variables. We then compared 341 classifying models (1 to 5 variables combinations × 11 classifier algorithms) according to mean squared error, logloss, sensitivity, specificity, precision, accuracy, area under curve of the ROC-curves and F1-score. F1-score ranged from 0.823 for the best 1-variable model to a maximum of 0.947 for the 4-variables best model. Most specific and precise models included sd_HR, SD2, and CorDim. In conclusion, we provided high performance classifying models able to distinguish diffuse from limited cutaneous SSc subtypes easy to perform at the bedside from ECG recording. Models were based on 1 to 5 HRV indexes used as nonlinear markers of autonomic integrated influences on cardiac activity.

Systemic sclerosis (SSc) is a rare and complex connective tissue disease associated with high morbidity and mortality. SSc is characterized by ischemic vasculopathy, cutaneous and visceral fibrosis and a dysimmune state (Denton and Khanna, 2017; Volkmann et al., 2023; Barnes and Mayes, 2012). We have derived induced pluripotent stem cell (iPSC) lines from two SSc patients aged 38 and 67 years with severe vascular phenotype. These iPSC lines expressed pluripotent markers, exhibited normal and stable genome, and differentiated into trilineage embryonic layers in teratoma formation assays. These SSc-specific iPSC lines can be differentiated into endothelial cells, providing a valuable model to elucidate vascular dysfunction and develop personalized therapeutic approaches.

Adipose tissue is recognized as a valuable source of cells with angiogenic, immunomodulatory, reparative and antifibrotic properties and emerged as a therapeutic alternative for the regeneration and repair of damaged tissues. The use of adipose-tissue-based therapy is expanding in autoimmune diseases, particularly in Systemic Sclerosis (SSc), a disease in which hands and face are severely affected, leading to disability and a decrease in quality of life. Combining the advantage of an abundant supply of fat tissue and a high abundance of stem/stromal cells, fat grafting and adipose tissue-derived cell-based therapies are attractive therapeutic options in SSc. This review aims to synthesize the evidence to determine the effects of the use of these biological products for face and hands treatment in the context of SSc. This highlights several points: the need to use relevant effectiveness criteria taking into account the clinical heterogeneity of SSc in order to facilitate assessment and comparison of innovative therapies; second, it reveals some impacts of the disease on fat-grafting success; third, an important heterogeneity was noticed regarding the manufacturing of the adipose-derived products and lastly, it shows a lack of robust evidence from controlled trials comparing adipose-derived products with standard care.