Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.
Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.
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DOI：
10.1001/jamaneurol.2014.999
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发表时间：
2014-08
期刊：
影响因子：
29
通讯作者：
Lancaster, Eric
中科院分区：
文献类型：
--
作者：
Greene, Maxwell;Lai, Yongjie;Baella, Nicolle;Dalmau, Josep;Lancaster, Eric
抗Tr免疫应答与副肿瘤性小脑变性（PCD）和霍奇金淋巴瘤（HL）相关。一个病例系列报道了Delta/Notch样表皮生长因子相关受体（DNER）是抗Tr抗体的实际靶点，但这一结果尚未得到复制。描述1例抗Tr患者，并证实DNER是一系列抗Tr患者的自身抗原。在宾夕法尼亚大学医院对DNER抗体的生物样本进行观察性研究和分析。我们检查了1例抗Tr患者的脑脊液样本和5例抗Tr患者的血清和/或脑脊液样本。使用先前用于检测人DNER抗体的质粒转染HEK 293 T和HELA细胞以表达与增强的绿色荧光蛋白标签偶联的DNER。36岁男性，患有小脑发育异常变性和抗Tr，接受皮质类固醇和静脉注射免疫球蛋白治疗，导致化疗前临床改善。尽管进行了密切的肿瘤学随访、活检和PET/CT扫描，但直到症状发作后6个月，他才被诊断为HL。这名患者的脑脊液与转染表达DNER的细胞反应，另外5名副肿瘤性小脑变性、HL和抗Tr患者的CSF和/或血清也发生反应。5份血清样品中只有4份与透化细胞反应，足以与背景区分开来，但所有5份血清样品都令人信服地标记了活细胞，其背景明显较少。所有6份对照血清样本和1份来自先前标记为抗Tr（但无HL或小脑炎）的患者的血清样本均不识别DNER。本病例证明了小脑变性患者抗Tr免疫反应检测的重要性。抗Tr抗体与HL的强相关性需要对该肿瘤进行仔细监测。我们还证实DNER是Tr免疫应答的靶抗原。与固定的透化细胞的免疫染色相比，针对活转染细胞筛选DNER抗体可以提供改善的信噪比特征。
The anti-Tr immune response is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin’s lymphoma (HL). One case series has reported that the Delta/Notch-like epidermal growth factor-related receptor (DNER) is the actual target for anti-Tr antibodies, but this result has not been replicated. To describe a patient with anti-Tr and confirm that DNER is the autoantigen for a series of patients with anti-Tr. Observational study and analysis of biological samples for antibodies to DNER at the Hospital of the University of Pennsylvania. We examined a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or cerebrospinal fluid samples from 5 other patients with anti-Tr. Transfection of HEK293T and HELA cells to express DNER coupled to an enhanced green fluorescent protein tag using a plasmid previously used to detect human DNER antibodies. 36-year-old man with pareneoplastic cerebellar degeneration and anti-Tr underwent treatment with corticosteroids and intravenous immunoglobulin, resulting in clinical improvement prior to chemotherapy. Despite close oncological follow up, a biopsy and PET/CT scanning, he was not diagnosed with HL until 6 months after symptom onset. The cerebrospinal fluid from this patient reacted with cells transfected to express DNER, as did CSF and/or sera from 5 other patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of 5 sera samples reacted to permeabilized cells enough to be distinguished from background, but all 5 sera samples convincingly labelled live cells, which had considerably less background. All 6 control sera samples and 1 sera sample from a patient previously labeled as anti-Tr (but without HL or cerebellitis) did not recognize DNER. This case demonstrates the importance of testing for the anti-Tr immune response in patients with cerebellar degeneration. The strong association of anti-Tr with HL requires careful surveillance for this tumor. We also confirm that DNER is the target antigen of the Tr immune response. Screening for DNER antibodies against living transfected cells may be offer an improved signal-to-noise characteristic compared to immunostaining of fixed, permeabilized cells.
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影响因子：
3.4
作者：
Moscato, Emilia H.;Jain, Ankit;Balice-Gordon, Rita J.
通讯作者：
Balice-Gordon, Rita J.
影响因子：
11.2
作者：
de Graaff, Esther;Maat, Peter;Smitt, Peter Sillevis
通讯作者：
Smitt, Peter Sillevis
影响因子：
64.5
作者：
Kopan R;Ilagan MX
通讯作者：
Ilagan MX
DOI：
10.1523/jneurosci.0167-10.2010
发表时间：
2010-04-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Hughes EG;Peng X;Gleichman AJ;Lai M;Zhou L;Tsou R;Parsons TD;Lynch DR;Dalmau J;Balice-Gordon RJ
通讯作者：
Balice-Gordon RJ
影响因子：
4.8
作者：
Eiraku, M;Hirata, Y;Kengaku, M
通讯作者：
Kengaku, M