Alloimmunisation to Donor Antigens and Immune Rejection Following Foetal Neural Grafts to the Brain in Patients with Huntington's Disease.
Identifieur interne : 000057 ( Hal/Curation ); précédent : 000056; suivant : 000058Alloimmunisation to Donor Antigens and Immune Rejection Following Foetal Neural Grafts to the Brain in Patients with Huntington's Disease.
Auteurs : Pierre Krystkowiak [France] ; Véronique Gaura [France] ; Myriam Labalette [France] ; Amandine Rialland [France] ; Philippe Remy [France] ; Marc Peschanski [France] ; Anne-Catherine Bachoud-Lévi [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2007.
English descriptors
Abstract
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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
Url:
DOI: 10.1371/journal.pone.0000166
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<idno type="DOI">10.1371/journal.pone.0000166</idno>
<series><title level="j">PLoS ONE</title>
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<profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Huntington's disease</term>
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<front><div type="abstract" xml:lang="en">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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.</div>
</front>
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<hal api="V3"> <titleStmt> <title xml:lang="en">Alloimmunisation to Donor Antigens and Immune Rejection Following Foetal Neural Grafts to the Brain in Patients with Huntington's Disease.</title>
<title xml:lang="en" type="sub">Immune rejection in the brain</title>
<author role="aut"> <persName> <forename type="first">Pierre</forename>
<surname>Krystkowiak</surname>
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<author role="aut"> <persName> <forename type="first">Véronique</forename>
<surname>Gaura</surname>
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<idno type="halauthorid">139281</idno>
<affiliation ref="#struct-93273"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Myriam</forename>
<surname>Labalette</surname>
</persName>
<idno type="halauthorid">139282</idno>
<affiliation ref="#struct-22470"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Amandine</forename>
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<author role="aut"> <persName> <forename type="first">Philippe</forename>
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<author role="crp"> <persName> <forename type="first">Marc</forename>
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<email type="domain">istem.genethon.fr</email>
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<author role="aut"> <persName> <forename type="first">Anne-Catherine</forename>
<surname>Bachoud-Lévi</surname>
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<email type="md5">403cf44695510a2cfe26b60ab9d1b59e</email>
<email type="domain">istem.genethon.fr</email>
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<funder>These results have been obtained as an ancillary study to the MIG-HD clinical trial (Multicentric Intracerebral Grafting in Huntington's Disease, NCT00190450) sponsored by Assistance-Publique/Hôpitaux de Paris, with additional support from Association Française contre les Myopathies and INSERM.</funder>
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<sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Alloimmunisation to Donor Antigens and Immune Rejection Following Foetal Neural Grafts to the Brain in Patients with Huntington's Disease.</title>
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<author role="aut"> <persName> <forename type="first">Pierre</forename>
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<author role="aut"> <persName> <forename type="first">Myriam</forename>
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<author role="aut"> <persName> <forename type="first">Amandine</forename>
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<author role="aut"> <persName> <forename type="first">Philippe</forename>
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<abstract xml:lang="en">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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.</abstract>
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