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Autoantibodies in autoimmune polyglandular syndrome type I patients react with major brain neurotransmitter systems
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Autoimmuna sjukdomar (Kämpe))
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2009 (English)In: Journal of Comparative Neurology, ISSN 0021-9967, E-ISSN 1096-9861, Vol. 513, no 1, 1-20 p.Article, review/survey (Refereed) Published
Abstract [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 gamma-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.

Place, publisher, year, edition, pages
2009. Vol. 513, no 1, 1-20 p.
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Medical and Health Sciences
URN: urn:nbn:se:uu:diva-106864DOI: 10.1002/cne.21913ISI: 000262558700001PubMedID: 19107747OAI: oai:DiVA.org:uu-106864DiVA: diva2:227019
Available from: 2009-07-08 Created: 2009-07-07 Last updated: 2016-05-09Bibliographically approved

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