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 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. This article is protected by copyright. All rights reserved.