Detection of High-Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins

Co-occurring anti-tripartite motif-containing protein 9 and 67 autoantibodies (TRIM9/67-IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67-IgG detection are not known. We performed a retrosp...

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Bibliographic Details
Published in:Annals of neurology 2023-12, Vol.94 (6), p.1086-1101
Main Authors: Bartley, Christopher M, Ngo, Thomas T, Do, Le Duy, Zekeridou, Anastasia, Dandekar, Ravi, Muñiz-Castrillo, Sergio, Alvarenga, Bonny D, Zorn, Kelsey C, Tubati, Asritha, Pinto, Anne-Laurie, Browne, Weston D, Hullett, Patrick W, Terrelonge, Mark, Schubert, Ryan D, Piquet, Amanda L, Yang, Binxia, Montalvo, Mayra, Kung, Andrew F, Mann, Sabrina A, Shah, Maulik P, Geschwind, Michael D, Gelfand, Jeffrey M, DeRisi, Joseph L, Pittock, Sean J, Honnorat, Jérôme, Pleasure, Samuel J, Wilson, Michael R
Format: Article
Language:English
Subjects:
Antibodies
Assaying
Autoantibodies
Autoantibodies - cerebrospinal fluid
Biomarkers
Biomarkers - cerebrospinal fluid
Biopsy
Cancer
Cerebellum
Cerebrospinal fluid
Encephalitis
Humans
Immunofluorescence
Immunoglobulin G
Immunoprecipitation
Metastases
Nerve Tissue Proteins - metabolism
Paraneoplastic Cerebellar Degeneration
Phage display
Proteins
Retrospective Studies
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Summary:Co-occurring anti-tripartite motif-containing protein 9 and 67 autoantibodies (TRIM9/67-IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67-IgG detection are not known. We performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67-IgG cases by tissue-based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell-based assay (CBA), and immunoblot. Cases in which TRIM9/67-IgG was detected by at least 2 assays were considered TRIM9/67-IgG positive. Among these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67-IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. TRIM9/67-IgG is a rare but likely high-risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086-1101.
ISSN:0364-5134
1531-8249
DOI:10.1002/ana.26776