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

针对TRIM9和TRIM67蛋白的高危副肿瘤抗体检测

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作者: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, Binxia Yang, Mayra Montalvo, Andrew

Methods

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.

Objective

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

Results

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. Interpretation: 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.

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