ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD.
ZSCAN1 Autoantibodies Are Associated with Pediatric Paraneoplastic ROHHAD.
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DOI：
10.1002/ana.26380
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发表时间：
2022-08
影响因子：
11.2
通讯作者：
DeRisi, Joseph L.
中科院分区：
文献类型：
--
作者：
Mandel-Brehm, Caleigh;Benson, Leslie A.;Tran, Baouyen;Kung, Andrew F.;Mann, Sabrina A.;Vazquez, Sara E.;Retallack, Hanna;Sample, Hannah A.;Zorn, Kelsey C.;Khan, Lillian M.;Kerr, Lauren M.;McAlpine, Patrick L.;Zhang, Lichao;McCarthy, Frank;Elias, Joshua E.;Katwa, Umakanth;Astley, Christina M.;Tomko, Stuart;Dalmau, Josep;Seeley, William W.;Pleasure, Samuel J.;Wilson, Michael R.;Gorman, Mark P.;DeRisi, Joseph L.
快速发作的肥胖伴下丘脑功能障碍、通气不足和自主神经失调 (ROHHAD) 是一种病因不明的严重儿科疾病，可导致下丘脑功能障碍和频繁的猝死。神经母细胞肿瘤的频繁并发引起了对自身免疫性副肿瘤神经综合征（PNS）的怀疑；然而，特异性抗神经自身抗体（PNS 的标志）尚未被发现。我们的目标是确定自身免疫性副肿瘤病因是否是 ROHHAD 的基础。使用人肽组可编程噬菌体展示 (PhIP-Seq) 筛选儿科 ROHHAD 患者 (n = 9)、非炎症个体 (n = 100) 和相关儿科对照 (n = 25) 的免疫球蛋白 G (IgG)。使用放射性配体结合和基于细胞的测定法对假定的 ROHHAD 特异性自身抗体进行了正交验证。分别使用免疫组织化学和质谱法评估 ROHHAD 肿瘤和健康脑组织中自身抗体靶标的表达。通过 PhIP-Seq 在 ROHHAD 患者中检测到 ZSCAN1 自身抗体，并使用放射性配体结合和基于细胞的测定在 7/9 ROHHAD 患者和 0/125 对照中进行正交验证。证实了ZSCAN1在ROHHAD肿瘤和健康人脑组织中的表达。我们的结果支持这样的观点，即肿瘤相关的 ROHHAD 综合征是一种小儿 PNS，可能是由对周围神经母细胞肿瘤的免疫反应引发的。 ZSCAN1 自身抗体可能有助于早期、准确地诊断 ROHHAD 综合征，从而提供早期检测和治疗的方法。这项工作需要后续研究来测试新型诊断测试的敏感性和特异性。最后，鉴于啮齿类动物缺乏 ZSCAN1 基因，我们的研究强调了基于人类的方法检测新型 PNS 亚型的价值。安神经学 2022 年；92：279–291
Rapid‐onset Obesity with Hypothalamic Dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD), is a severe pediatric disorder of uncertain etiology resulting in hypothalamic dysfunction and frequent sudden death. Frequent co‐occurrence of neuroblastic tumors have fueled suspicion of an autoimmune paraneoplastic neurological syndrome (PNS); however, specific anti‐neural autoantibodies, a hallmark of PNS, have not been identified. Our objective is to determine if an autoimmune paraneoplastic etiology underlies ROHHAD. Immunoglobulin G (IgG) from pediatric ROHHAD patients (n = 9), non‐inflammatory individuals (n = 100) and relevant pediatric controls (n = 25) was screened using a programmable phage display of the human peptidome (PhIP‐Seq). Putative ROHHAD‐specific autoantibodies were orthogonally validated using radioactive ligand binding and cell‐based assays. Expression of autoantibody targets in ROHHAD tumor and healthy brain tissue was assessed with immunohistochemistry and mass spectrometry, respectively. Autoantibodies to ZSCAN1 were detected in ROHHAD patients by PhIP‐Seq and orthogonally validated in 7/9 ROHHAD patients and 0/125 controls using radioactive ligand binding and cell‐based assays. Expression of ZSCAN1 in ROHHAD tumor and healthy human brain tissue was confirmed. Our results support the notion that tumor‐associated ROHHAD syndrome is a pediatric PNS, potentially initiated by an immune response to peripheral neuroblastic tumor. ZSCAN1 autoantibodies may aid in earlier, accurate diagnosis of ROHHAD syndrome, thus providing a means toward early detection and treatment. This work warrants follow‐up studies to test sensitivity and specificity of a novel diagnostic test. Last, given the absence of the ZSCAN1 gene in rodents, our study highlights the value of human‐based approaches for detecting novel PNS subtypes. ANN NEUROL 2022;92:279–291
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影响因子：
11.2
作者：
Lai, Meizan;Hughes, Ethan G.;Peng, Xiaoyu;Zhou, Lei;Gleichman, Amy J.;Shu, Huidy;Mata, Sabrina;Kremens, Daniel;Vitaliani, Roberta;Geschwind, Michael D.;Bataller, Luis;Kalb, Robert G.;Davis, Rebecca;Graus, Francesc;Lynch, David R.;Balice-Gordon, Rita;Dalmau, Josep
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Dalmau, Josep
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8
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Paz-Priel, Ido
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3.2
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Giacomozzi, Claudio;Guaraldi, Federica;Cutrera, Renato
通讯作者：
Cutrera, Renato
影响因子：
56.9
作者：
Dehal, P;Predki, P;Stubbs, L
通讯作者：
Stubbs, L
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3.8
作者：
Huppke, Peter;Heise, Alexander;Gaertner, Jutta
通讯作者：
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