{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:59:29Z","timestamp":1791413969435,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T00:00:00Z","timestamp":1515542400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R25 NS065745"],"award-info":[{"award-number":["R25 NS065745"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS077851"],"award-info":[{"award-number":["R01 NS077851"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["K08 NS075142"],"award-info":[{"award-number":["K08 NS075142"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001068","name":"Dana Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001068","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the pathogenic mechanisms of autoantibodies to the cell adhesion molecule Caspr2 in acquired neuromyotonia and autoimmune encephalitis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Caspr2\u2010positive samples were confirmed using a cell\u2010based assay, and their IgG subtypes were determined by enzyme\u2010linked immunosorbent assay and cell\u2010based assay. A solid phase binding assay quantified the binding of Caspr2 to contactin\u20102 in the presence of Caspr2 autoantibodies. Living cultures of primary rat hippocampal neurons were incubated with Caspr2\u2010positive or control sera, and the distribution of Caspr2\u2010positive immunofluorescent puncta and total surface Caspr2 was quantified. HEK cells transfected to express Caspr2 were incubated with Caspr2\u2010positive or control samples, and cell\u2010surface biotinylation and Western blot were used to assess total, internalized, and surface levels of Caspr2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We confirmed 6 samples with strong Caspr2 reactivity. IgG4 Caspr2 antibodies were present in all 6 cases. Caspr2 interacted with another cell adhesion molecule, contactin\u20102, with nanomolar affinity in the solid phase assay, and Caspr2 autoantibodies inhibited this interaction. Caspr2 autoantibodies did not affect the surface expression of Caspr2 in rat primary hippocampal neurons or transfected HEK cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Caspr2 autoantibodies inhibit the interaction of Caspr2 with contactin\u20102 but do not cause internalization of Caspr2. Functional blocking of cell adhesion molecule interactions represents a potential mechanism with therapeutic implications for IgG4 autoantibodies to cell adhesion molecules in neurological diseases. Ann Neurol 2018;83:40\u201051<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25120","type":"journal-article","created":{"date-parts":[[2017,12,16]],"date-time":"2017-12-16T21:47:22Z","timestamp":1513460842000},"page":"40-51","source":"Crossref","is-referenced-by-count":120,"title":["Mechanisms of <scp>C<\/scp>aspr2 antibodies in autoimmune encephalitis and neuromyotonia"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-6869","authenticated-orcid":false,"given":"Kristina R.","family":"Patterson","sequence":"first","affiliation":[{"name":"Department of Neurology Hospital of the University of Pennsylvania Philadelphia PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Dalmau","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital of the University of Pennsylvania Philadelphia PA"},{"name":"Hospital Clinic\u2010August Pi i Sunyer Biomedical Research Institute (IDIBAPS) University of Barcelona 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