Immune response after striatal engraftment of fetal neuronal cells in patients with Huntington's disease: Consequences for cerebral transplantation programs

Objectives: Striatal transplantation of human fetal neurones as a therapeutic approach to treat Huntington's disease is under investigation. The allogeneic graft material raises questions of immune response and immunosuppressive treatment. No data is available on how the human brain reacts immunologically over time to neuronal transplantation. Methods: We measured post-engraftment immune responses as assessed by the development of anti-human leukocyte antigen (HLA)-antibodies to allogeneic intrastriatal transplantation of fetal neurons in Huntington's disease patients. Results: Out of 10 patients without HLA-antibodies before engraftment, five developed HLA-antibodies of class I and II. The time between transplantation and development of HLA-antibodies was variable, with detection either immediately after engraftment, during immunosuppressive therapy or months to years after immunosuppressive drugs were discontinued. There are no typical changes in magnetic resonance imaging that distinguish the different immune behaviors. Positive clinical responses to engraftment might not be reflected in the F-deoxyglucose positron emission tomography images as expected. Conclusions: There is indeed an immune response from the human brain, but the time between transplantation and development of anti-HLA-antibodies is variable and unpredictable. A long-term, post-engraftment immunosuppressant therefore cannot be justified. The impact of the emergence of HLA-antibodies on graft survival and clinical efficacy cannot be ascertained at this stage. Given the projected clinical trials of cell transplantation in neurodegenerative disorders, the findings are of practical significance.