Spontaneous and tetracosactide-induced anti-ACTH antibodies in man.
Spontaneous and tetracosactide-induced anti-ACTH antibodies in man.
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DOI：
10.1111/cen.12795
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发表时间：
2016-04
影响因子：
3.2
通讯作者：
Pearce SH
中科院分区：
文献类型：
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作者：
Gan EH;MacArthur K;Mitchell AL;Joshi A;Crock P;Pearce SH
在一项定期注射二十四交酯贮库型制剂的临床试验中，13例自身免疫性阿狄森病（AAD）患者中有4例在注射二十四交酯后立即出现不良反应。我们希望研究这些不良反应是否可能是由于循环中抗二十四碳交酯（ACTH 1 -24）抗体的产生。使用免疫印迹法和ELISA法研究了来自试验参与者（n = 13;基线和暴露于二十四碳交酯后）、131例不相关AAD患者、92例Graves病（GD）患者、15例孤立性ACTH缺乏症患者和102例对照者血清的抗ACTH结合活性。还使用合并血清进行人垂体组织切片的免疫组织化学。在暴露于二十四碳交酯的13例试验患者（包括所有发生不良反应的患者）的血清中，有10例（77%）发现了分别对应于ACTH 1 -24和全长ACTH 1 -39的约4和6 kDa条带。这与健康对照血清相反，健康对照血清显示无结合。同样的10名受试者通过ELISA也显示出高水平的与二十四碳丙交酯的结合，沿着有21%的AAD患者、14%的GD患者（与对照相比均P <0.001）和1名孤立的ACTH缺乏症患者（15名中的7%）。这些血清也承认在人垂体部分的天然ACTH。我们的研究表明，重复给予贮库型二十四碳丙交酯可导致抗ACTH 1 -24自身反应性。此外，大量AAD和GD患者也具有相似的自发抗ACTH反应性。这些抗体的存在可能介导一些不良反应或解释对慢性ACTH治疗的耐药现象。
During a clinical trial of regular tetracosactide depot injections, four of 13 patients with autoimmune Addison's disease (AAD) developed adverse reactions immediately following tetracosactide injections. We wished to investigate whether these adverse effects could be due to the production of circulating antitetracosactide (ACTH1–24) antibodies. Anti‐ACTH binding activity was investigated using immunoblotting and ELISA on sera from participants in the trial (n = 13; baseline and after tetracosactide exposure), 131 unrelated patients with AAD, 92 patients with Graves’ disease (GD), 15 patients with isolated ACTH deficiency and 102 controls. Immunohistochemistry of human pituitary tissue sections was also performed using pooled sera. Bands at approximately 4 and 6 kDa, corresponding to ACTH1–24 and full‐length ACTH1–39, respectively, were found in 10 of 13 (77%) of sera from trial patients exposed to tetracosactide, including all those who had an adverse reaction. This is in contrast with healthy control sera, which showed no binding. The same 10 subjects also showed high levels of binding to tetracosactide by ELISA, along with 21% of patients with AAD, 14% of patients with GD (both P < 0·001 compared to controls) and 1 isolated ACTH deficiency patient (7% of 15). These sera also recognized native ACTH in human pituitary sections. Our study demonstrates that repeated administration of depot tetracosactide can lead to anti‐ACTH1–24 autoreactivity. In addition, a significant number of patients with AAD and GD also had similar, spontaneous, anti‐ACTH reactivity. The presence of these antibodies could mediate some of the adverse effects or explain the well‐described phenomenon of resistance to chronic ACTH therapy.