Immunotherapeutic rescue of steroidogenic function in autoimmune Addison's disease: Pilot Study

自身免疫性阿狄森氏病是一种慢性疾病，由人体免疫系统攻击并最终破坏肾上腺引起。这会导致某些类固醇激素的缺乏，这些激素对生命和健康至关重要，健康的肾上腺通常会产生这些激素。目前治疗阿狄森氏病的方法只是用药片代替缺失的肾上腺类固醇激素。这使人们感觉更好，但往往不能完全恢复正常，并使他们长期依赖类固醇药物（每天2或3剂），有几个长期的副作用，以及预期寿命缩短。我们计划采用一种全新的方法来治疗艾迪生氏病，即尝试关闭免疫系统，从而停止对肾上腺的攻击。我们将使用一种安全但有效的治疗方法，称为利妥昔单抗，它可以从血液和组织中清除某种称为B淋巴细胞的免疫细胞。在过去的10年里，这种治疗方法已被用于100多万患有血液病的人，并以两次4小时的输液方式进行，间隔14天。利妥昔单抗治疗其他几种自身免疫性疾病的结果显示出巨大的希望，疾病得到了实质性的改善。由于已知肾上腺组织具有很强的再生能力，一旦免疫攻击消失，剩余的（未被破坏的）肾上腺细胞很可能会再生，恢复重要类固醇激素的分泌。当肾上腺分泌不足或低于必要水平时，人体自然会产生一种肾上腺刺激激素，ACTH-促肾上腺皮质激素。艾迪生的人有非常高水平的促肾上腺皮质激素，这将导致肾上腺再生一旦免疫攻击已被删除。这一策略可能首次导致自身免疫性阿狄森氏病的永久治愈。

Autoimmune Addison`s disease is a chronic disease caused by the body`s immune system attacking and eventually destroying the adrenal glands. This causes deficiency of certain steroid hormones that are essential for life and wellbeing, which the healthy adrenal glands normally produce. The current approach to treating Addison`s disease is simply to replace the missing adrenal steroid hormones using tablets. This makes people feel better, but often not fully back to normal and leaves them chronically dependent upon steroid medications (2 or 3 doses daily), with several long-term side effects, as well as a reduced life-expectancy. We plan a radical new approach to treatment of Addison`s disease, which is to try to switch off the immune system, so the attack on the adrenal glands ceases. We will use a safe but powerful treatment called rituximab that removes a certain type of immune cell, called the B lymphocyte, from the bloodstream and tissues. This treatment has been used on more than a million people with blood conditions over the last 10 years, and is given as two 4-hour infusions, 14 days apart. The results of rituximab therapy in several other autoimmune disease show great promise, with substantial amelioration of disease. As adrenal tissue is already known to have a great capacity for regeneration, it is highly likely that the remaining (not destroyed) adrenal cells will regenerate, restoring the secretion of the vital steroid hormones to normal, once the immune attack has gone. The body naturally makes an adrenal gland stimulating hormone, ACTH-adrenocorticotropic hormone, when adrenal secretions are deficient or below the necessary levels. People with Addison`s have very high levels of ACTH, and this would cause the regeneration of the adrenal glands once the immune attack has been removed. This strategy could lead to a permanent cure of autoimmune Addison s disease, for the first time.