PT  - JOURNAL ARTICLE
AU  - Cristina Valencia-Sanchez
AU  - Andrew M Knight
AU  - M Bakri Hammami
AU  - Yong Guo
AU  - John R Mills
AU  - Thomas J Kryzer
AU  - Amanda L Piquet
AU  - Anik Amin
AU  - Morgan Heinzelmann
AU  - Claudia F Lucchinetti
AU  - Vanda A Lennon
AU  - Andrew McKeon
AU  - Sean J Pittock
AU  - Divyanshu Dubey
TI  - Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome
AID  - 10.1136/jnnp-2021-326656
DP  - 2022 Feb 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 196--200
VI  - 93
IP  - 2
4099  - http://jnnp.bmj.com/content/93/2/196.short
4100  - http://jnnp.bmj.com/content/93/2/196.full
SO  - J Neurol Neurosurg Psychiatry2022 Feb 01; 93
AB  - 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 25–87). 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.