{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:36:10Z","timestamp":1794281770676,"version":"4.9.0"},"reference-count":11,"publisher":"BMJ","issue":"2","funder":[{"DOI":"10.13039\/100014535","name":"Mayo Clinic Center for Individualized Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014535","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Archived sera\/cerebrospinal fluid (CSF) were evaluated by tissue-based immunofluorescence assay to identify patients with identical axon initial segment (AIS)-specific staining pattern. Phage immunoprecipitation sequencing (PhIP-Seq) was used to identify the putative autoantigen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IgG in serum (17) and\/or CSF (16) from 25 patients yielded unique AIS-specific staining on murine central nervous system (CNS) tissue. An autoantibody specific for TRIM46 was identified by PhIP-Seq, and autoantigen specificity was confirmed by transfected COS7 cell-based assay. Clinical information was available for 22 TRIM46-IgG seropositive patients. Fifteen were female (68%). Median age was 67 years (range 25\u201387). Fifteen (68%) patients presented with subacute cerebellar syndrome (six isolated; nine with CNS accompaniments: encephalopathy (three), brainstem signs (two), myelopathy (two), parkinsonism (one)). Other phenotypes included limbic encephalitis (three), encephalopathy with\/without seizures (two), myelopathy (two). Eighteen (82%) had cancer: neuroendocrine carcinomas (9; pancreatic (3), small-cell lung (4), oesophagus (1), endometrium (1)), adenocarcinomas (6; lung (2), ovarian (2), endometrial (1), breast (1)), sarcoma (2) and gastrointestinal tumour (1). Neurological symptoms in three followed immune checkpoint inhibitor (ICI) administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jnnp-2021-326656","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T18:26:05Z","timestamp":1639765565000},"page":"196-200","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome"],"prefix":"10.1136","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0116-8035","authenticated-orcid":false,"given":"Cristina","family":"Valencia-Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M","family":"Knight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-5163","authenticated-orcid":false,"given":"M Bakri","family":"Hammami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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A","family":"Lennon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6856-8143","authenticated-orcid":false,"given":"Andrew","family":"McKeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6140-5584","authenticated-orcid":false,"given":"Sean J","family":"Pittock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divyanshu","family":"Dubey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"2022070104101216000_93.2.196.1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.neulet.2009.10.031","article-title":"A new paraneoplastic encephalomyelitis autoantibody reactive with the axon initial segment","volume":"467","author":"Shams'ili","year":"2009","journal-title":"Neurosci Lett"},{"key":"2022070104101216000_93.2.196.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.012"},{"key":"2022070104101216000_93.2.196.3","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1002\/acn3.396","article-title":"Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes","volume":"4","author":"van Coevorden-Hameete","year":"2017","journal-title":"Ann Clin Transl Neurol"},{"key":"2022070104101216000_93.2.196.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-018-0025-6"},{"key":"2022070104101216000_93.2.196.5","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1856"},{"key":"2022070104101216000_93.2.196.6","doi-asserted-by":"crossref","DOI":"10.1212\/NXI.0000000000001014","article-title":"Updated diagnostic criteria for paraneoplastic neurologic syndromes","volume":"8","author":"Graus","year":"2021","journal-title":"Neurol Neuroimmunol 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