Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis
Rabphilin-3A as a Targeted Autoantigen in Lymphocytic Infundibulo-neurohypophysitis
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DOI：
10.1210/jc.2014-4209
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发表时间：
2015-07-01
影响因子：
5.8
通讯作者：
Oiso, Yutaka
中科院分区：
文献类型：
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作者：
Iwama, Shintaro;Sugimura, Yoshihisa;Oiso, Yutaka
背景：中枢性尿崩症（CDI）可由多种疾病引起，但约一半患者的病因诊断仍不清楚。淋巴细胞性基底-神经垂体炎（LINH）在特发性CDI病例中越来越被认可；然而，与其他垂体疾病包括肿瘤的鉴别诊断可能是困难的，因为类似的临床和放射表现。明确诊断LINH需要有创性垂体活检。目的：本研究旨在鉴定LINH的自身抗原，从而建立一种基于血清自身抗体的诊断方法。设计：用从LINH患者或对照组血清中纯化的igg免疫沉淀大鼠垂体后叶裂解液。免疫沉淀采用液相色谱-串联质谱法筛选垂体自身抗原。随后，我们制备候选自身抗原重组蛋白，并用Western blotting分析血清中的自身抗体。结果：Rabphilin-3A被证明是最有诊断价值的自身抗原。29例LINH患者中有22例（76%）检测到抗rabphilin- 3a抗体，18例淋巴细胞性腺垂体炎患者中有2例（11.1%）检测到抗rabphilin- 3a抗体。相比之下，活检证实无淋巴细胞性垂体炎的鞍/鞍上肿块患者（n = 34）没有这些抗体，包括18例CDI患者。rabphilin - 3a在垂体后叶和下丘脑垂体后叶加压素神经元中表达，而在垂体前叶中不表达。结论：rabphilin-3A是LINH的主要自身抗原。rabphilin-3A自身抗体可作为LINH诊断的生物标志物，并可用于CDI患者的鉴别诊断。
Context: Central diabetes insipidus (CDI) can be caused by several diseases, but in about half of the patients the etiological diagnosis remains unknown. Lymphocytic infundibulo-neurohypophysitis (LINH) is an increasingly recognized entity among cases of idiopathic CDI; however, the differential diagnosis from other pituitary diseases including tumors can be difficult because of similar clinical and radiological manifestations. The definite diagnosis of LINH requires invasive pituitary biopsy.Objective: The study was designed to identify the autoantigen(s) in LINH and thus develop a diagnostic test based on serum autoantibodies.Design: Rat posterior pituitary lysate was immunoprecipitated with IgGs purified from the sera of patients with LINH or control subjects. The immunoprecipitates were subjected to liquid chromatographytandem mass spectrometry to screen for pituitary autoantigens of LINH. Subsequently, we made recombinant proteins of candidate autoantigens and analyzed autoantibodies in serum by Western blotting.Results: Rabphilin-3A proved to be the most diagnostically useful autoantigen. Anti-rabphilin-3A antibodies were detected in 22 of the 29 (76%) patients (including 4 of the 4 biopsy-proven samples) with LINH and 2 of 18 (11.1%) patients with biopsy-proven lymphocytic adeno-hypophysitis. In contrast, these antibodies were absent in patients with biopsy-proven sellar/suprasellar masses without lymphocytic hypophysitis (n = 34), including 18 patients with CDI. Rabphilin-3Awas expressed in posterior pituitary and hypothalamic vasopressin neurons but not anterior pituitary.Conclusions: These results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH and be useful for the differential diagnosis in patients with CDI.