Detection of High‐Risk Paraneoplastic Antibodies Against TRIM9 and TRIM67 proteins
Christopher M. Bartley, Thomas T. Ngo, Le Duy Do, Anastasia Zekeridou, Ravi Dandekar, Sergio Muñiz‐Castrillo, Bonny D. Alvarenga, Kelsey C. Zorn, Asritha Tubati, Anne‐Laurie Pinto, Weston D. Browne, Patrick W. Hullett, Mark Terrelonge, Ryan D. Schubert, Amanda L. Piquet, Yang Binxia, Mayra J. Montalvo Perero, Andrew F. Kung, Sabrina A. Mann, Maulik P. Shah, Michael D. Geschwind, Jeffrey M. Gelfand, Joseph L. DeRisi, Sean J. Pittock, Jérôme Honnorat, Samuel J. Pleasure, Michael R. Wilson - Neurology (clinical)
- Neurology
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, multi‐center study to evaluate the cerebrospinal fluid (CSF) and serum of candidate TRIM9/67‐IgG cases by tissue‐based immunofluorescence (TBIF), peptide phage display immunoprecipitation sequencing (PhIP‐Seq), overexpression cell‐based assay (CBA), and immunoblot. Cases in whom TRIM9/67‐IgG was detected by at least two 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 ten, 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 are rare but likely high‐risk paraneoplastic biomarkers for which CBA appears to be the most sensitive diagnostic assay.
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