[Immunoablation or otherwise followed by hematopoietic cell stem as intensive treatment of severe autoimmune diseases].
The treatment of severe autoimmune diseases has been recently revitalized by the increasing utilization of clinical interventions aimed at ablating/abrogating autoimmune lymphoid clones followed (but not in certain procedures) by transplantation of allogeneic, but also autologous, hematopoietic stem cells. Two different investigative avenues have paved the way to specific clinical studies. The first originates from the epochal murine experiments of the '70s, and has been greatly expanded in the last decade. A graft-versus-autoimmunity effect could also be demonstrated. In addition, it could also be shown that induced experimental autoimmune diseases such as adjuvant arthritis and autoimmune encephalomyelitis could, surprisingly, be cured following autologous transplantation. The first results in humans were observational and derived from studies including patients with coincidental diseases (severe autoimmune diseases plus leukemia/aplasia) treated with allogeneic hematopoietic stem cell transplants. Although the concept of an allogeneic transplant is indisputably more appealing, very few patients with an isolated severe autoimmune disease have been treated using such a therapeutic approach. Reduced intensity conditioned transplants relying on subsequent graft-versus-autoimmunity effects strengthened by donor lymphocyte infusions are being explored cautiously. On the other hand, autologous transplants are being performed quite extensively. To date, transplanted severe autoimmune diseases include multiple sclerosis, connective tissue diseases (systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis) and many others. It is uncertain if the main mechanism is solely immunoablative, or whether tolerized lymphocytes may also develop during a postulated "window of opportunity" following the transplant.
du Haut Champ
Alberto M Marmont
AM
Dipartimento di Emato-Oncologia, Azienda Ospedaliera e Cliniche Convenzionate S. Martino di Genova.
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007165:Immunosuppression Therapy; D012720:Severity of Illness Index