Novel autoantigens in autoimmune hypophysitis
Novel autoantigens in autoimmune hypophysitis
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DOI：
10.1111/j.1365-2265.2008.03180.x
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发表时间：
2008-08-01
影响因子：
3.2
通讯作者：
Caturegli, Patrizio
中科院分区：
文献类型：
--
作者：
Lupi, Isabella;Broman, Karl W.;Caturegli, Patrizio
背景 垂体自身抗体见于自身免疫性垂体炎和其他疾病。它们是垂体自身免疫的标志物，但目前临床价值有限。用于检测的方法缺乏足够的灵敏度和特异性，主要是因为致病性垂体自身抗原尚不清楚，因此尚未开发出基于抗原的免疫测定法。 目的本研究旨在在蛋白质组学测定中使用血清作为探针来鉴定新型垂体自身抗原。我们还比较了免疫印迹和免疫荧光方法诊断自身免疫性垂体炎的准确性。 研究设计和受试者 将来自自身免疫性垂体炎病例的 28 份血清（14 份经组织学证实，14 份临床怀疑）与来自对照的 98 份血清进行比较，其中包括 14 名垂体腺瘤患者、48 名自身免疫性甲状腺炎患者（15 名格雷夫斯病患者和 33 名患者）。桥本氏甲状腺炎）和 36 名健康受试者。方法所有血清均针对通过一维 (1D) 凝胶电泳分离的人垂体胞质蛋白进行测试。对条带识别进行统计分析以检测垂体炎血清优先识别的分子量区域。然后使用二维凝胶免疫印迹和质谱法对感兴趣的蛋白质点进行测序。还通过免疫荧光测试了血清对猕猴垂体切片的识别。结果 与健康受试者 (P = 0.004) 或垂体腺瘤患者 (P = 0.044) 相比，垂体炎病例更容易识别 25-27 kDa 范围内的单个区域。该区域包含两种新的候选自身抗原：14 号染色体开放阅读框 166 (C14orf166) 和绒毛膜生长激素。在预测经组织学证实的垂体炎方面，25-27-kDa 区域的免疫印迹阳性结果比免疫荧光具有更高的敏感性（64% 与 57%）和特异性（86% 与 76%），尽管其性能仍不足以使免疫印迹成为临床上有用的测试。 结论 该研究报道了两种可作为自身免疫性垂体炎自身抗原的新型蛋白质。需要进一步的研究来验证其致病作用和诊断效用。
Background Pituitary autoantibodies are found in autoimmune hypophysitis and other conditions. They are a marker of pituitary autoimmunity but currently have limited clinical value. The methods used for their detection lack adequate sensitivity and specificity, mainly because the pathogenic pituitary autoantigen(s) are not known and therefore antigen-based immunoassays have not been developed.Objectives This study aimed to identify novel pituitary autoantigens using sera as probes in proteomic assays. We also compared immunoblotting and immunofluorescence methods for their accuracy in diagnosing autoimmune hypophysitis.Study design and subjects Twenty-eight sera from autoimmune hypophysitis cases (14 histologically proven and 14 clinically suspected) were compared to 98 sera from controls, which included 14 patients with pituitary adenomas, 48 with autoimmune thyroiditis (15 Graves' disease and 33 Hashimoto's thyroiditis) and 36 healthy subjects.Methods All sera were tested against human pituitary cytosolic proteins separated by one-dimensional (1D) gel electrophoresis. The band recognition was analysed statistically to detect molecular weight regions preferentially recognized by hypophysitis sera. 2D gel immunoblotting and mass spectrometry were then used to sequence the protein spots of interest. Sera were also tested by immunofluorescence for their recognition of Macaca mulatta pituitary sections.Results A single region in the 25-27-kDa range was recognized more often by hypophysitis cases than healthy subjects (P = 0.004) or patients with pituitary adenomas (P = 0.044). This region contained two novel candidate autoantigens: chromosome 14 open reading frame 166 (C14orf166) and chorionic somatomammotrophin. Immunoblotting positivity for the 25-27-kDa region yielded greater sensitivity (64% vs. 57%) and specificity (86% vs. 76%) than immunofluorescence in predicting histologically proven hypophysitis, although the performance was still inadequate to make immunoblotting a clinically useful test.Conclusion The study reports two novel proteins that could act as autoantigens in autoimmune hypophysitis. Further studies are needed to validate their pathogenic role and diagnostic utility.