Photo Credit: Meletios Verras

The following is a summary of “Dermal cellular senescence and EndMT in patients with systemic sclerosis undergoing cyclophosphamide or aHSCT treatment,” published in the December 2024 issue of Rheumatology by Chiu et al. 

Cellular senescence and endothelial-to-mesenchymal transition (EndMT) are profibrotic processes involved in systemic sclerosis (SSc). How they respond to treatment is largely unknown. 

Researchers conducted a retrospective study on cellular senescence and EndMT in SSc treatments.  

They collected skin biopsies from patients with diffuse cutaneous SSc (dcSSc) in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial who underwent autologous hematopoietic stem cell transplantation (aHSCT) or cyclophosphamide pulse (iv CYC) treatment, before and 6 months after randomization. They examined fibrosis, inflammation, senescence, EndMT, and tissue remodeling through histopathology. 

The results showed that 14 pairs of skin biopsies were analyzed. The decrease in modified Rodnan skin score (mRSS) was greater in patients treated with aHSCT (median change -14 [IQR -16 to -9]) compared with iv CYC (median change -6 [IQR -9 to -4], P = 0.028). uPAR on fibroblasts, P21 on vessels, and EndMT decreased after treatment in both groups, with more pronounced reductions in the aHSCT group. Poor skin response was linked to high baseline CTGF on fibroblasts (odds ratio (OR) 1.43) and low baseline P21 on vessels (OR 0.41). Poor response was also correlated with increases in CTGF (OR 1.29) and P21 (OR 3.02) after treatment (P < 0.001). 

Investigators found that both aHSCT and iv CYC reduced skin thickening and attenuated EndMT in dcSSc, with no significant difference in cellular senescence. EndMT and uPAR were linked to fibro-remodeling, while senescence, CTGF, uPAR, and vascularity were associated with treatment response. 

Source: academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keae660/7916572