Wulffraat N M, Drexhage H A, Bottazzo G F, Wiersinga W M, Jeucken P, Van der Gaag R
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 1989 Aug;69(2):231-8. doi: 10.1210/jcem-69-2-231.
The presence of serum immunoglobulins (Ig) blocking ACTH-induced adrenal DNA synthesis and/or cortisol production was studied in 25 patients with idiopathic Addison's disease. For this purpose guinea pig adrenal segments kept in organ culture were exposed to ACTH and graded concentrations of patient IgG. After a 5-h culture period the cortisol present in the culture fluid was measured by RIA, and DNA synthesis in the adrenal cells was measured using Feulgen densitometry on frozen sections of the cultured adrenal segments. Addition of ACTH alone in concentrations of 0.1-10 pmol/L to the culture system stimulated in vitro cortisol secretion; the maximal stimulation was 63 +/- 35% (+/- SD; n = 5) at a concentration 0.1 pmol/L. ACTH also increased (in concentrations of 1 fmol/L to 1 pmol/L) the percentage of fasciculata cells in S-phase from 0-4% (nonstimulated) to 5-12%. IgG preparations from all but 2 of the 25 patients with idiopathic Addison's disease blocked these in vitro ACTH-induced adrenal responses in a dose-dependent fashion. IgG from 2 patients with tuberculous adrenalitis, 1 patient with secondary adrenal insufficiency, and 7 normal subjects had no blocking activity. Among 5 non-Addisonian autoimmune endocrinopathy patients who had adrenal cytoplasmic autoantibodies, 4 had no ACTH-blocking IgGs. Two of 9 patients with miscellaneous adrenal disorders (Cushing's disease, pigmented adrenal micronodular dysplasia, and adrenal nodules) had ACTH-blocking activity. These results demonstrate the existence of IgGs blocking the in vitro effects of ACTH and suggest their involvement in the pathogenesis of idiopathic Addison's disease.
对25例特发性Addison病患者血清免疫球蛋白（Ig）阻断促肾上腺皮质激素（ACTH）诱导的肾上腺DNA合成和/或皮质醇产生的情况进行了研究。为此，将器官培养中的豚鼠肾上腺切片暴露于ACTH和不同浓度的患者IgG中。培养5小时后，用放射免疫分析法（RIA）测定培养液中存在的皮质醇，并使用福尔根密度测定法对培养的肾上腺切片冰冻切片测量肾上腺细胞中的DNA合成。向培养系统中单独添加浓度为0.1 - 10 pmol/L的ACTH可刺激体外皮质醇分泌；在0.1 pmol/L浓度时最大刺激为63±35%（±标准差；n = 5）。ACTH还可使束状带细胞处于S期的百分比从0 - 4%（未刺激）增加到5 - 12%（浓度为1 fmol/L至1 pmol/L）。25例特发性Addison病患者中除2例之外，其余患者的IgG制剂均以剂量依赖方式阻断这些体外ACTH诱导的肾上腺反应。2例结核性肾上腺炎患者、1例继发性肾上腺功能不全患者以及7名正常受试者的IgG无阻断活性。5例患有肾上腺细胞质自身抗体的非Addison自身免疫性内分泌病患者中，4例没有ACTH阻断性IgG。9例患有其他肾上腺疾病（库欣病、色素沉着性肾上腺微小结节发育异常和肾上腺结节）的患者中有2例具有ACTH阻断活性。这些结果证明存在阻断ACTH体外作用的IgG，并提示它们参与特发性Addison病的发病机制。
