Changing winds in refractory autoimmune disease in children: clearing the road for tolerance with cellular therapies

To give an overview of the recent advances in cellular therapies in pediatric autoimmune diseases.

Since the 1990s, autologous hematopoietic stem cell transplantation (HSCT) has been applied in more than 800 patients with severe refractory autoimmune diseases. Despite obvious successes, it is clear that the autoimmune disease in many of these patients relapsed. Anecdotal reports of allogeneic HSCT seem promising. Furthermore, several trials exploring the use of mesenchymal stem or stromal cells (MSC) for therapy of refractory autoimmune diseases have been published. Mostly allogeneic MSC are used at a dose of 1 million/kg intravenously.

Even though promising new agents have become available for the treatment of autoimmune disease (AID), some arthritis patients fail to achieve even a modest improvement. Cellular therapies may be the answer in steering the immune system into a more tolerant path. Autologous HSCT after an immunoablative pretreatment allows rebuilding of a partially reset immune system. A small group of severely refractory pediatric patients is unlikely to benefit from immunosuppressive therapies alone. With allogeneic transplant becoming safer and overall mortality numbers much lower in pediatric transplantation, allogeneic HSCT might become the more sensible option for this small group of refractory patients. A promising new cellular therapy is the use of MSC. The working mechanism is immunomodulatory, through induction of Tregs. Although their place is still to be determined, they may provide a safer alternative to severely compromised children or as an adjuvant therapy earlier in the disease. We have implemented cellular therapy options for our refractory pediatric AID patients. We consider progressing to cellular therapies in severely affected individuals, to ultimately cure their disease. Our cellular therapy protocols are provided in this review.