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Cerebellum. 2019 Apr;18(2):245-254. doi: 10.1007/s12311-018-0987-5.

TRIM9 and TRIM67 Are New Targets in Paraneoplastic Cerebellar Degeneration.

Author information

1
French Reference Center for Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, F-69677, Bron, France.
2
Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon - Université Claude Bernard Lyon 1, F-69372, Lyon, France.
3
University of Lyon, Université Claude Bernard Lyon 1, Lyon, F-69372, Lyon, France.
4
Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, 27516, USA.
5
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan.
6
University Grenoble Alpes, CEA, Inserm, BIG-BGE, 38000, Grenoble, France.
7
Neurochemistry Unit, Biochemistry Department, Hospices Civils de Lyon, Groupement Hospitalier Est, Bron, France.
8
Immunology department, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre-Bénite, France.
9
French Reference Center for Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, F-69677, Bron, France. jerome.honnorat@chu-lyon.fr.
10
Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon - Université Claude Bernard Lyon 1, F-69372, Lyon, France. jerome.honnorat@chu-lyon.fr.
11
University of Lyon, Université Claude Bernard Lyon 1, Lyon, F-69372, Lyon, France. jerome.honnorat@chu-lyon.fr.
12
Neuro-Oncologie, Hôpital Neurologique Pierre Wertheimer, 59 Boulevard Pinel, 69677, Bron Cedex, France. jerome.honnorat@chu-lyon.fr.

Abstract

To describe autoantibodies (Abs) against tripartite motif-containing (TRIM) protein 9 and 67 in two patients with paraneoplastic cerebellar degeneration (PCD) associated with lung adenocarcinoma. Abs were characterized using immunohistochemistry, Western blotting, cultures of murine cortical, and hippocampal neurons, immunoprecipitation, mass spectrometry, knockout mice for Trim9 and 67, and cell-based assay. Control samples included sera from 63 patients with small cell lung cancer without any paraneoplastic neurological syndrome, 36 patients with lung adenocarcinoma and PNS, CSF from 100 patients with autoimmune encephalitis, and CSF from 165 patients with neurodegenerative diseases. We found Abs targeting TRIM9 and TRIM67 at high concentration in the serum and the cerebrospinal fluid (CSF) of a 78-year-old woman and a 65-year-old man. Both developed subacute severe cerebellar ataxia. Brain magnetic resonance imaging found no abnormality and no cerebellar atrophy. Both had CSF inflammation with mild pleiocytosis and a few oligoclonal bands. We identified a pulmonary adenocarcinoma, confirming the paraneoplastic neurological syndrome in both patients. They received immunomodulatory and cancer treatments without improvement of cerebellar ataxia, even though both were in remission of their cancer (for more than 10 years in one patient). Anti-TRIM9 and anti-TRIM67 Abs were specific to these two patients. All control serum and CSF samples tested were negative for anti-TRIM9 and 67. Anti-TRIM9 and anti-TRIM67 Abs appeared to be specific biomarkers of PCD and should be added to the panel of antigens tested when this is suspected.

KEYWORDS:

Autoantibodies; Lung cancer; Paraneoplastic cerebellar disorders; TRIM67; TRIM9

PMID:
30350014
PMCID:
PMC6445697
[Available on 2019-10-01]
DOI:
10.1007/s12311-018-0987-5
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances, Supplementary concept, Grant support

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