Characterisation of TRIM46 autoantibody-associated paraneoplastic neurological syndrome

Cristina Valencia-Sanchez, Andrew M. Knight, M. Bakri Hammami, Yong Guo, John R. Mills, Thomas J. Kryzer, Amanda L. Piquet, Anik Amin, Morgan Heinzelmann, Claudia F. Lucchinetti, Vanda A. Lennon, Andrew McKeon, Sean J. Pittock, Divyanshu Dubey

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 25-87). 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.

Original languageEnglish (US)
Pages (from-to)196-200
Number of pages5
JournalJournal of neurology, neurosurgery, and psychiatry
Volume93
Issue number2
DOIs
StatePublished - Feb 1 2022

Keywords

  • neuroimmunology
  • paraneoplastic syndrome

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

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