ORIGINAL ARTICLE Immune response after striatal engraftment of fetal neuronal cells in patients with Huntington’s disease: Consequences for cerebral transplantation programs Simone S. Krebs, 1,2 Michael Trippel, 1 Thomas Prokop, 1 Talib N. Omer, 1 Bernard Landwehrmeyer, 3 Wolfgang A. Weber 2 and Guido Nikkhah 1 Departments of 1 Stereotactical Neurosurgery and 2 Nuclear Medicine, Faculty of Medicine, University of Freiburg, Freiburg, and 3 Department of Neurology, Faculty of Medicine, University of Ulm, Ulm, Germany Introduction Presently, no disease-modifying therapies are avail- able for Huntington’s disease (HD), and the symp- tomatic treatments have their limitations. One approach under consideration is the use of fetal cell transplantation into the striatum as cell replacement strategy. Unilateral 1,2 and bilateral 3,4 striatal trans- plantation of fetal-derived neuronal cells have undergone clinical assessment. There are still many open questions about the immunological interac- tion between the host and cell-derived transplants in the human brain. The brain was considered an immunologically privileged site for transplantation. What we know today is that this privilege is not absolute. 5,6 Animal studies and post-mortem exam- inations of fetal mesencephalon-derived grafts in HD recipients (independent of the post-transplant Keywords brain’s immune response; cerebral engraftment; Huntington’s disease Correspondence Simone S. Krebs MD, Department of Nuclear Medicine, Medical Faculty, University of Freiburg, Germany Tel: +49-761-270-3888 Fax: +49-761-270-3930 Email: simone.krebs@uniklinik-freiburg.de Received: 24 July 2010; received: 14 December 2010; accepted: 17 December 2010. Abstract 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 immunologi- cally 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 transplanta- tion 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 18 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-antibod- ies is variable and unpredictable. A long-term, post-engraftment immuno- suppressant 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 neuro- degenerative disorders, the findings are of practical significance. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759-1961.2011.00018.x, May 2011) Clinical and Experimental Neuroimmunology 2 (2011) 25–32 ª 2011 Japanese Society for Neuroimmunology 25 Clinical & Experimental Neuroimmunology