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.
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DOI: 10.1371/journal.pone.0000166
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Paris 11</orgName> <orgName type="acronym">UP11</orgName> <desc> <address> <addrLine>Bâtiment 300 - 91405 Orsay cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-psud.fr/</ref> </desc></org></tutelle><tutelle name="URA2210" active="#struct-441569" type="direct"><org type="institution" xml:id="struct-441569" status="VALID"><idno type="IdRef">02636817X</idno><idno type="ISNI">0000000122597504</idno><orgName>Centre National de la Recherche Scientifique</orgName><orgName type="acronym">CNRS</orgName><date type="start">1939-10-19</date><desc><address><country key="FR"></country></address><ref type="url">http://www.cnrs.fr/</ref></desc></org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Peschanski, Marc" sort="Peschanski, Marc" uniqKey="Peschanski M" first="Marc" last="Peschanski">Marc Peschanski</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-2837" status="OLD"> <orgName>Neuroplasticité et thérapeutique</orgName> <desc> <address> <addrLine>Faculte de Médecine 8, Rue du General Sarrail 94010 CRETEIL CEDEX</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.im3.inserm.fr/formations/unites_INSERM/U421</ref> </desc> <listRelation> <relation name="U421" active="#struct-303623" type="direct"></relation> <relation active="#struct-420786" type="direct"></relation> </listRelation><tutelles><tutelle name="U421" active="#struct-303623" type="direct"><org type="institution" xml:id="struct-303623" status="VALID"> <idno type="IdRef">026388278</idno> <orgName>Institut National de la Santé et de la Recherche Médicale</orgName> <orgName type="acronym">INSERM</orgName> <desc> <address> <addrLine>101, rue de Tolbiac, 75013 Paris </addrLine> <country key="FR"></country> </address> <ref type="url">http://www.inserm.fr</ref> </desc></org></tutelle><tutelle active="#struct-420786" type="direct"><org type="institution" xml:id="struct-420786" status="VALID"> <orgName>Université Paris-Est Créteil Val-de-Marne - Paris 12</orgName> <orgName type="acronym">UPEC UP12</orgName> <desc> <address> <addrLine>61 avenue du Général de Gaulle - 94010 Créteil cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-pec.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author><author><name sortKey="Bachoud Levi, Anne Catherine" sort="Bachoud Levi, Anne Catherine" uniqKey="Bachoud Levi A" first="Anne-Catherine" last="Bachoud-Lévi">Anne-Catherine Bachoud-Lévi</name><affiliation wicri:level="1"><hal:affiliation type="laboratory" xml:id="struct-22471" status="VALID"> <orgName>Service de neurologie [Mondor]</orgName> <desc> <address> <addrLine>51, av du Maréchal de Tassigny, 94010 Créteil Cedex</addrLine> <country key="FR"></country> </address> </desc> <listRelation> <relation active="#struct-300068" type="direct"></relation> <relation active="#struct-300087" type="direct"></relation> <relation active="#struct-420786" type="direct"></relation> </listRelation><tutelles><tutelle active="#struct-300068" type="direct"><org type="institution" xml:id="struct-300068" status="VALID"> <orgName>Assistance publique - Hôpitaux de Paris (AP-HP)</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle><tutelle active="#struct-300087" type="direct"><org type="institution" xml:id="struct-300087" status="VALID"> <orgName>Hôpital Henri Mondor</orgName> <desc> <address> <country key="FR"></country> </address> </desc></org></tutelle><tutelle active="#struct-420786" type="direct"><org type="institution" xml:id="struct-420786" status="VALID"> <orgName>Université Paris-Est Créteil Val-de-Marne - Paris 12</orgName> <orgName type="acronym">UPEC UP12</orgName> <desc> <address> <addrLine>61 avenue du Général de Gaulle - 94010 Créteil cedex</addrLine> <country key="FR"></country> </address> <ref type="url">http://www.u-pec.fr/</ref> </desc></org></tutelle></tutelles></hal:affiliation><country>France</country></affiliation></author></analytic><idno type="DOI">10.1371/journal.pone.0000166</idno><series><title level="j">PLoS ONE</title><idno type="ISSN">1932-6203</idno><imprint><date type="datePub">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="mix" xml:lang="en"><term>Huntington's disease</term><term>immune rejection</term><term>intracerebral graft</term></keywords></textClass></profileDesc></teiHeader><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></TEI><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> </persName> <idno type="halauthorid">139280</idno> <affiliation ref="#struct-94723"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Véronique</forename> <surname>Gaura</surname> </persName> <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> <surname>Rialland</surname> </persName> <idno type="halauthorid">139283</idno> <affiliation ref="#struct-22471"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philippe</forename> <surname>Remy</surname> </persName> <idno type="halauthorid">139284</idno> <affiliation ref="#struct-93273"></affiliation> <affiliation ref="#struct-22471"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Marc</forename> <surname>Peschanski</surname> </persName> <email type="md5">403cf44695510a2cfe26b60ab9d1b59e</email> <email type="domain">istem.genethon.fr</email> <idno type="halauthorid">139285</idno> <affiliation ref="#struct-2837"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Anne-Catherine</forename> <surname>Bachoud-Lévi</surname> </persName> <email type="md5">92bfdad2c1429348e45e1fd36d9c4a0d</email> <email type="domain">gmail.com</email> <idno type="halauthorid">635747</idno> <affiliation ref="#struct-22471"></affiliation> <affiliation ref="#struct-2837"></affiliation> </author> <editor role="depositor"> <persName> <forename>Marc</forename> <surname>Peschanski</surname> </persName> <email type="md5">403cf44695510a2cfe26b60ab9d1b59e</email> <email type="domain">istem.genethon.fr</email> </editor> <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> </titleStmt> <editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2007-01-26 09:25:42</date> <date type="whenModified">2017-01-04 16:21:15</date> <date type="whenReleased">2007-01-02 14:57:03</date> <date type="whenProduced">2007</date> <date type="whenEndEmbargoed">2007-01-26</date> <ref type="file" target="http://www.hal.inserm.fr/inserm-00108216/document"> <date notBefore="2007-01-26"></date> </ref> <ref type="file" n="1" target="http://www.hal.inserm.fr/inserm-00108216/file/ImmunBrain_PLoSOne_final_3_.pdf"> <date notBefore="2007-01-26"></date> </ref> </edition> <respStmt> <resp>contributor</resp> <name key="113817"> <persName> <forename>Marc</forename> <surname>Peschanski</surname> </persName> <email type="md5">403cf44695510a2cfe26b60ab9d1b59e</email> <email type="domain">istem.genethon.fr</email> </name> </respStmt> </editionStmt> <publicationStmt> <distributor>CCSD</distributor> <idno type="halId">inserm-00108216</idno> <idno type="halUri">http://www.hal.inserm.fr/inserm-00108216</idno> <idno type="halBibtex">krystkowiak:inserm-00108216</idno> <idno type="halRefHtml">PLoS ONE, Public Library of Science, 2007, 2, pp.e166. <10.1371/journal.pone.0000166></idno> <idno type="halRef">PLoS ONE, Public Library of Science, 2007, 2, pp.e166. <10.1371/journal.pone.0000166></idno> </publicationStmt> <seriesStmt> <idno type="stamp" n="INSERM">INSERM - Institut national de la santé et de la recherche médicale</idno> <idno type="stamp" n="CNRS">CNRS - Centre national de la recherche scientifique</idno> <idno type="stamp" n="CEA">CEA - Commissariat à l'énergie atomique</idno> <idno type="stamp" n="APHP" p="INSERM">AP-HP</idno> <idno type="stamp" n="UPEC" p="CV_UPEC">Université Paris-Est Créteil Val-de-Marne</idno> <idno type="stamp" n="UPEC-UPEM">UPEC-UPEM</idno> </seriesStmt> <notesStmt> <note type="audience" n="1">Not set</note> <note type="popular" n="0">No</note> <note type="peer" n="1">Yes</note> </notesStmt> <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> <title xml:lang="en" type="sub">Immune rejection in the brain</title> <author role="aut"> <persName> <forename type="first">Pierre</forename> <surname>Krystkowiak</surname> </persName> <idno type="halauthorid">139280</idno> <affiliation ref="#struct-94723"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Véronique</forename> <surname>Gaura</surname> </persName> <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> <surname>Rialland</surname> </persName> <idno type="halauthorid">139283</idno> <affiliation ref="#struct-22471"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Philippe</forename> <surname>Remy</surname> </persName> <idno type="halauthorid">139284</idno> <affiliation ref="#struct-93273"></affiliation> <affiliation ref="#struct-22471"></affiliation> </author> <author role="crp"> <persName> <forename type="first">Marc</forename> <surname>Peschanski</surname> </persName> <email type="md5">403cf44695510a2cfe26b60ab9d1b59e</email> <email type="domain">istem.genethon.fr</email> <idno type="halauthorid">139285</idno> <affiliation ref="#struct-2837"></affiliation> </author> <author role="aut"> <persName> <forename type="first">Anne-Catherine</forename> <surname>Bachoud-Lévi</surname> </persName> <email type="md5">92bfdad2c1429348e45e1fd36d9c4a0d</email> <email type="domain">gmail.com</email> <idno type="halauthorid">635747</idno> <affiliation ref="#struct-22471"></affiliation> <affiliation ref="#struct-2837"></affiliation> </author> </analytic> <monogr> <idno type="halJournalId" status="VALID">28700</idno> <idno type="issn">1932-6203</idno> <title level="j">PLoS ONE</title> <imprint> <publisher>Public Library of Science</publisher> <biblScope unit="volume">2</biblScope> <biblScope unit="pp">e166</biblScope> <date type="datePub">2007</date> <date type="dateEpub">2007-01-24</date> </imprint> </monogr> <idno type="doi">10.1371/journal.pone.0000166</idno> <idno type="pubmed">17245442</idno> </biblStruct> </sourceDesc> <profileDesc> <langUsage> <language ident="en">English</language> </langUsage> <textClass> <keywords scheme="author"> <term xml:lang="en">immune rejection</term> <term xml:lang="en">Huntington's disease</term> <term xml:lang="en">intracerebral graft</term> </keywords> <classCode scheme="halDomain" n="sdv.bc">Life Sciences [q-bio]/Cellular Biology</classCode> <classCode scheme="halTypology" n="ART">Journal articles</classCode> </textClass> <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> </profileDesc> </hal></record>Pour manipuler ce document sous Unix (Dilib)
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