Autologous hematopoietic stem cell transplantation in systemic sclerosis: A reset to tolerance?

Abstract

Autologous hematopoietic stem cell transplantation (ASCT) is an effective therapy for refractory autoimmune disease, in particular diffuse cutaneous systemic sclerosis (dcSSc). ASCT is the only treatment that can induce long term remission in dcSSc. However, the mechanism of action of ASCT has not yet been fully elucidated. The current hypothesis is that ASCT induces a long term 'reset' of the immune system, but there is no clear definition yet of such an immunological 'reset to tolerance', nor has it been established how to distinguish a 'reset' from long term immunosuppression. Here, we review the literature on immunological changes after ASCT in dcSSc patients to gain more insight whether changes in immunological parameters can help elucidate the mechanism of action of ASCT. We identified 12 studies. While some immunological parameters could be correlated to clinical response, heterogeneity in the studies, short follow-up time and the small sample sizes preclude firm conclusions. Importantly, most patients displayed a sustained clinical response despite the presence of auto-antibodies or higher-than-normal concentrations of cytokines and proteins associated with disease activity. This suggests that the mechanism of ASCT may not be solely immunological. Future research should focus on larger cohorts of patients and also take functional evaluation of immune cells into account in order to determine whether ASCT induces long term immunosuppression or resets the immune system to tolerance. Answering this question is key to further optimizing ASCT for dcSSc patients.