PURPOSE OF REVIEW: To give an overview of the recent advances in cellular therapies in pediatric autoimmune diseases. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: To give an overview of the recent advances in cellular therapies in pediatric autoimmune diseases. RECENT FINDINGS: 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. SUMMARY: Even though promising new agents have become available for the treatment of autoimmune disease (AID), some arthritispatients 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.
Authors: Eveline M Delemarre; Sarah T A Roord; Theo van den Broek; Evelien Zonneveld-Huijssoon; Wilco de Jager; Henk Rozemuller; Anton C Martens; Femke Broere; Nico M Wulffraat; Tibor T Glant; Berent J Prakken; Femke van Wijk Journal: Arthritis Rheumatol Date: 2014-02 Impact factor: 10.995
Authors: Joost F Swart; Eveline M Delemarre; Femke van Wijk; Jaap-Jan Boelens; Jürgen Kuball; Jacob M van Laar; Nico M Wulffraat Journal: Nat Rev Rheumatol Date: 2017-02-23 Impact factor: 20.543
Authors: Markus G Seidel; Tatjana Hirschmugl; Laura Gamez-Diaz; Wolfgang Schwinger; Nina Serwas; Andrea Deutschmann; Gregor Gorkiewicz; Werner Zenz; Christian Windpassinger; Bodo Grimbacher; Christian Urban; Kaan Boztug Journal: J Allergy Clin Immunol Date: 2014-12-22 Impact factor: 10.793
Authors: Hema Chaplin; Lewis Carpenter; Anni Raz; Elena Nikiphorou; Heidi Lempp; Sam Norton Journal: Rheumatology (Oxford) Date: 2021-08-02 Impact factor: 7.580