Apoptosis plays a key role in clonal selection of pathologic fibroblast sub‐populations in systemic sclerosis

Abstract

Systemic sclerosis or scleroderma (SSc), is an autoimmune disease with an incidence of 20 people per million and per year in USA. No cure for SSc is currently available so, after a debilitating phase, death is frequently the outcome of this disease with a higher risk of mortality among Afro‐Americans and women. Causes of SSc are unknown for now but various factors seem to be involved like genetics or exposure to chemical or virus. One of the features of this disease is extracellular matrix excessive deposition which affect not only skin but also internal organs. Despite heterogeneity of cellular and molecular responses of fibroblasts (Fb), a larger proportion of SSc Fb express higher level of collagen than in normal ones. So, many groups postulated that SSc lesions could result from clonal expansion of a Fb sub‐population with a higher capacity to proliferate and/or a better resistance to apoptosis. Dermal Fb populations from 17 French‐Canadian volunteers (4 healthy and 13 SSc affected) were tested for proliferation and apoptosis parameters. We have found that SSc Fb proliferate with a lower rate than the normal one, excluding proliferation as a clonal selection origin. Nevertheless lesional SSc Fb were less sensitive than normal Fb or non‐lesional SSc Fb to Fas pathway apoptosis allowing to hypothesize that clonal selection could be performed via apoptotic pathway. This work was supported by grants from CHIR and FRSQ.