@article {Valencia-Sanchez196, author = {Cristina Valencia-Sanchez and Andrew M Knight and M Bakri Hammami and Yong Guo and John R Mills and Thomas J Kryzer and Amanda L Piquet and Anik Amin and Morgan Heinzelmann and Claudia F Lucchinetti and Vanda A Lennon and Andrew McKeon and Sean J Pittock and Divyanshu Dubey}, title = {Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome}, volume = {93}, number = {2}, pages = {196--200}, year = {2022}, doi = {10.1136/jnnp-2021-326656}, publisher = {BMJ Publishing Group Ltd}, abstract = {Objectives To report the expanded neurological presentations and oncological associations of tripartite motif-containing protein 46 (TRIM46)-IgG seropositive patients.Methods 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.Results 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{\textendash}87). 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.Conclusions This study supports TRIM46-IgG being a biomarker of paraneoplastic CNS disorders and expands the neurological phenotypes, oncological and ICI-related adverse event associations.}, issn = {0022-3050}, URL = {https://jnnp.bmj.com/content/93/2/196}, eprint = {https://jnnp.bmj.com/content/93/2/196.full.pdf}, journal = {Journal of Neurology, Neurosurgery \& Psychiatry} }