Alloimmunisation to donor antigens and immune rejection following foetal neural grafts to the brain in patients with Huntington's disease.
BACKGROUND
The brain is deemed "immunologically privileged" due to sparse professional antigen-presenting cells and lymphatic drainage, and to the blood-brain barrier. Although the actual extent of this privilege is controversial, there is general consensus about the limited need in intracerebral neural grafts for immunosuppressive regimens comparable to those used in other cases of allotransplantation. This has led over the past fifteen years to the use of either short-term or even no immunosuppression in most clinical trials with foetal neural transplant in patients with Parkinson's and Huntington's disease.


RESULTS
We report biological demonstration of alloimmunisation without signs of rejection in four grafted patients out of 13 studied during the course of a clinical trial involving fetal neural transplantation in patients with Huntington's Disease. Biological, radiological and clinical demonstration of an ongoing rejection process was observed in a fifth transplanted patient. The rejection process was, however, fully reversible under immunosuppressive treatment and graft activity recovered within six months.


CONCLUSIONS
There had been, up to date, no report of documented cases that could have cast a doubt on those procedures. Our results underline the need for a reconsideration of the extent of the so-called immune privilege of the brain and of the follow-up protocols of patients with intracerebral grafts. It also suggests that some of the results obtained in past studies with foetal neural transplants may have been biased by an unrecognized immune response to donor cells.
Krystkowiak
Pierre
P
Department of Neurology and Movement Disorders, Equipe Associée 2683, Hospital R. Salengro, Regional University Hospital, Lille, France.
Gaura
Véronique
V
Labalette
Myriam
M
Rialland
Amandine
A
Remy
Philippe
P
Peschanski
Marc
M
Bachoud-Lévi
Anne-Catherine
AC
D000941:Antigens / Q000276:immunology*; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000601:surgery; D002986:Clinical Trials as Topic; D053686:Fetal Stem Cells; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006816:Huntington Disease / Q000276:immunology / Q000601:surgery*; D007114:Immunization; D007166:Immunosuppressive Agents / Q000276:immunology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D009474:Neurons / Q000276:immunology; D033581:Stem Cell Transplantation / Q000009:adverse effects; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D000941:Antigens; D006680:HLA Antigens; D007166:Immunosuppressive Agents