Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems
Identifieur interne : 000A09 ( Main/Exploration ); précédent : 000A08; suivant : 000A10Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems
Auteurs : Sergueï O. Fetissov [Suède] ; Sophie Bensing [Suède] ; Jan Mulder [Suède] ; Erwan Le Maitre [Suède] ; Anna Ena Hulting [Suède] ; Tibor Harkany [Suède] ; Olov Ekwall [Suède] ; Filip Sköldberg [Suède] ; Eystein S. Husebye [Norvège] ; Jaakko Perheentupa [Finlande] ; Fredrik Rorsman [Suède] ; Olle K Mpe [Suède] ; Tomas Hökfelt [Suède]Source :
- Journal of Comparative Neurology [ 0021-9967 ] ; 2009-03-01.
English descriptors
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Abstract
Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2008 Wiley‐Liss, Inc.
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DOI: 10.1002/cne.21913
Affiliations:
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Fetissov, ADEN Laboratory, Faculté de Médecine‐Pharmacie, 22, Bld Gambetta, Rouen, 76183 Cedex 1, FranceTomas Hökfelt, Department of Neuroscience, Karolinska Institutet, Retzius väg. 8, 17177, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Bensing, Sophie" sort="Bensing, Sophie" uniqKey="Bensing S" first="Sophie" last="Bensing">Sophie Bensing</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Mulder, Jan" sort="Mulder, Jan" uniqKey="Mulder J" first="Jan" last="Mulder">Jan Mulder</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Le Maitre, Erwan" sort="Le Maitre, Erwan" uniqKey="Le Maitre E" first="Erwan" last="Le Maitre">Erwan Le Maitre</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Hulting, Anna Ena" sort="Hulting, Anna Ena" uniqKey="Hulting A" first="Anna Ena" last="Hulting">Anna Ena Hulting</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Harkany, Tibor" sort="Harkany, Tibor" uniqKey="Harkany T" first="Tibor" last="Harkany">Tibor Harkany</name><affiliation wicri:level="3"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Biochemistry and Biophysics, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Ekwall, Olov" sort="Ekwall, Olov" uniqKey="Ekwall O" first="Olov" last="Ekwall">Olov Ekwall</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Sciences, University Hospital, Uppsala University, Uppsala</wicri:regionArea><wicri:noRegion>Uppsala</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Paediatrics, The Sahlgrenska Institute at Göteborg University, Göteborg</wicri:regionArea><wicri:noRegion>Göteborg</wicri:noRegion></affiliation></author><author><name sortKey="Skoldberg, Filip" sort="Skoldberg, Filip" uniqKey="Skoldberg F" first="Filip" last="Sköldberg">Filip Sköldberg</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Medical Sciences, University Hospital, Uppsala University, Uppsala</wicri:regionArea><wicri:noRegion>Uppsala</wicri:noRegion></affiliation></author><author><name sortKey="Husebye, Eystein S" sort="Husebye, Eystein S" uniqKey="Husebye E" first="Eystein S." last="Husebye">Eystein S. 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Fetissov, ADEN Laboratory, Faculté de Médecine‐Pharmacie, 22, Bld Gambetta, Rouen, 76183 Cedex 1, FranceTomas Hökfelt, Department of Neuroscience, Karolinska Institutet, Retzius väg. 8, 17177, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Comparative Neurology</title><title level="j" type="abbrev">J. Comp. Neurol.</title><idno type="ISSN">0021-9967</idno><idno type="eISSN">1096-9861</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2009-03-01">2009-03-01</date><biblScope unit="volume">513</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="1">1</biblScope><biblScope unit="page" to="20">20</biblScope></imprint><idno type="ISSN">0021-9967</idno></series><idno type="istex">755B989FDFD3B68B72695BA11BB585CB86F083F5</idno><idno type="DOI">10.1002/cne.21913</idno><idno type="ArticleID">CNE21913</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0021-9967</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>autoimmunity</term><term>dopamine</term><term>enzymes</term><term>monoamines</term><term>noradrenaline</term><term>serotonin</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Patients with autoimmune polyglandular syndrome type I (APS1) often display high titers of autoantibodies (autoAbs) directed against aromatic L‐amino acid decarboxylase (AADC), tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), and glutamic acid decarboxylase (GAD). Neurological symptoms, including stiff‐man syndrome and cerebellar ataxia, can occur in subjects with high levels of GAD autoAbs, particularly when patient sera can immunohistochemically stain γ‐aminobutyric acid (GABA) neurons. However, it was not known if APS1 sera can also stain major monoamine systems in the brain. Therefore, in this work we applied sera from 17 APS1 patients known to contain autoAbs against AADC, TH, TPH, and/or GAD to rat brain sections and processed the sections according to the sensitive immunohistochemical tyramide signal amplification method. We found that autoAbs in sera from 11 patients were able to stain AADC‐containing dopaminergic, serotonergic, and noradrenergic as well as AADC only (D‐group) neurons and fibers in the rat brain, in several cases with a remarkably high quality and sensitivity (dilution up to 1:1,000,000); and, since they are human antibodies, they offer a good opportunity for performing multiple‐labeling experiments using antibodies from other species. Six APS1 sera also stained GABAergic neuronal circuitries. Similar results were obtained in the mouse and primate brain. Our data demonstrate that many APS1 sera can immunostain the major monoamine and GABA systems in the brain. Only in a few cases, however, there was evidence that these autoAbs can be associated with neurological manifestations in APS1 patients, as, e.g., shown in previous studies in stiff‐man syndrome. J. Comp. Neurol. 513:1–20, 2009. © 2008 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Finlande</li><li>Norvège</li><li>Suède</li></country><region><li>Svealand</li></region><settlement><li>Stockholm</li></settlement></list><tree><country name="Suède"><region name="Svealand"><name sortKey="Fetissov, Serguei O" sort="Fetissov, Serguei O" uniqKey="Fetissov S" first="Sergueï O." last="Fetissov">Sergueï O. Fetissov</name></region><name sortKey="Bensing, Sophie" sort="Bensing, Sophie" uniqKey="Bensing S" first="Sophie" last="Bensing">Sophie Bensing</name><name sortKey="Ekwall, Olov" sort="Ekwall, Olov" uniqKey="Ekwall O" first="Olov" last="Ekwall">Olov Ekwall</name><name sortKey="Ekwall, Olov" sort="Ekwall, Olov" uniqKey="Ekwall O" first="Olov" last="Ekwall">Olov Ekwall</name><name sortKey="Fetissov, Serguei O" sort="Fetissov, Serguei O" uniqKey="Fetissov S" first="Sergueï O." last="Fetissov">Sergueï O. 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Husebye</name></noRegion></country><country name="Finlande"><noRegion><name sortKey="Perheentupa, Jaakko" sort="Perheentupa, Jaakko" uniqKey="Perheentupa J" first="Jaakko" last="Perheentupa">Jaakko Perheentupa</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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