检测高风险癌症相关TRIM9和TRIM67蛋白的抗体。
Detection of High-Risk Paraneoplastic Antibodies Against TRIM9 and TRIM67 proteins.
发表日期:2023 Aug 26
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, 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
来源:
ANNALS OF NEUROLOGY
摘要:
只有少数副肿瘤性小脑综合征病例中报告了、抗三重模体9和67含有蛋白特异性自身抗体(TRIM9/67-IgG)的共存情况。这些生物标志物的价值和TRIM9/67-IgG检测最敏感的方法尚不明确。我们进行了一项回顾性多中心研究,通过基于组织的荧光免疫技术(TBIF)、肽噬体展示免疫沉淀测序(PhIP-Seq)、过表达细胞实验(CBA)和免疫印迹技术,评估了候选TRIM9/67-IgG病例的脑脊液和血清。至少通过两种方法检测到TRIM9/67-IgG的病例被认为是TRIM9/67-IgG阳性。在这些病例中(N=13),CBA是最敏感的(100%),并显示所有病例都存在TRIM9和TRIM67自身抗体。根据可用临床病史的TRIM9/67-IgG病例中,亚急性小脑综合征是最常见的表现形式(N=7/10),其次是脑炎(N=3/10)。在这十例中,70%有合并癌症(7/10),其中85%(N=6/7)的癌症已经确定为转移性。所有可评估的癌症活检标本均表达TRIM9蛋白(N=5/5),其中4例的癌症区域组织中TRIM9的表达升高。TRIM9/67-IgG是罕见但可能是高危的副肿瘤性生物标志物,CBA似乎是最敏感的诊断方法。本文受版权保护。保留所有权利。
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.This article is protected by copyright. All rights reserved.