High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types

Medientyp: E-Artikel
Titel: High prevalence of NMDA receptor IgA/IgM antibodies in different dementia types
Beteiligte: Doss, Sarah; Wandinger, Klaus‐Peter; Hyman, Bradley T.; Panzer, Jessica A.; Synofzik, Matthis; Dickerson, Bradford; Mollenhauer, Brit; Scherzer, Clemens R.; Ivinson, Adrian J.; Finke, Carsten; Schöls, Ludger; Müller vom Hagen, Jennifer; Trenkwalder, Claudia; Jahn, Holger; Höltje, Markus; Biswal, Bharat B.; Harms, Lutz; Ruprecht, Klemens; Buchert, Ralph; Höglinger, Günther U.; Oertel, Wolfgang H.; Unger, Marcus M.; Körtvélyessy, Peter; Bittner, Daniel; [...]
Erschienen: Wiley, 2014
Erschienen in: Annals of Clinical and Translational Neurology
Sprache: Englisch
DOI: 10.1002/acn3.120
ISSN: 2328-9503
Entstehung:
Anmerkungen:
Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To retrospectively determine the frequency of <jats:italic>N</jats:italic>‐Methyl‐D‐Aspartate (<jats:styled-content style="fixed-case">NMDA</jats:styled-content>) receptor (<jats:styled-content style="fixed-case">NMDAR</jats:styled-content>) autoantibodies in patients with different forms of dementia.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Clinical characterization of 660 patients with dementia, neurodegenerative disease without dementia, other neurological disorders and age‐matched healthy controls combined with retrospective analysis of serum or cerebrospinal fluid (<jats:styled-content style="fixed-case">CSF</jats:styled-content>) for the presence of <jats:styled-content style="fixed-case">NMDAR</jats:styled-content> antibodies. Antibody binding to receptor mutants and the effect of immunotherapy were determined in a subgroup of patients.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Serum <jats:styled-content style="fixed-case">NMDAR</jats:styled-content> antibodies of IgM, IgA, or IgG subtypes were detected in 16.1% of 286 dementia patients (9.5% IgM, 4.9% IgA, and 1.7% IgG) and in 2.8% of 217 cognitively healthy controls (1.9% IgM and 0.9% IgA). Antibodies were rarely found in <jats:styled-content style="fixed-case">CSF</jats:styled-content>. The highest prevalence of serum antibodies was detected in patients with “unclassified dementia” followed by progressive supranuclear palsy, corticobasal syndrome, Parkinson's disease‐related dementia, and primary progressive aphasia. Among the unclassified dementia group, 60% of 20 patients had <jats:styled-content style="fixed-case">NMDAR</jats:styled-content> antibodies, accompanied by higher frequency of <jats:styled-content style="fixed-case">CSF</jats:styled-content> abnormalities, and subacute or fluctuating disease progression. Immunotherapy in selected prospective cases resulted in clinical stabilization, loss of antibodies, and improvement of functional imaging parameters. Epitope mapping showed varied determinants in patients with <jats:styled-content style="fixed-case">NMDAR</jats:styled-content> IgA‐associated cognitive decline.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Serum IgA/IgM <jats:styled-content style="fixed-case">NMDAR</jats:styled-content> antibodies occur in a significant number of patients with dementia. Whether these antibodies result from or contribute to the neurodegenerative disorder remains unknown, but our findings reveal a subgroup of patients with high antibody levels who can potentially benefit from immunotherapy.</jats:p></jats:sec>
Zugangsstatus: Freier Zugang

Nur in Feld suchen:

Zuletzt gesuchte Begriffe: