Adams D D, Knight J G, Manning P, Smith G
Faculty of Medicine, University of Otago, Dunedin, New Zealand.
J Clin Lab Immunol. 2004;53:13-25.
The aetiology of schizophrenia and the other psychoses is not yet established. The Knight model, based on genetic and other evidence, proposes that schizophrenia is an autoimmune disease, caused by the development of forbidden clones of B lymphocytes that secrete autoantibodies that accidentally stimulate cell surface receptors on certain neurons, affecting the limbic system of the brain. An unusual defect in a Maori man with Graves' disease rendered him unresponsive to the usually effective antithyroid drugs, prompting his being treated with prednisone, a non-specific immunosuppressant agent. This was highly successful, reducing the blood level of the causative thyroid-stimulating autoantibodies with reduction of thyroid hormone levels and thyroid gland size. Unfortunately, high dosage prednisone can be used for only a month, because of steroid toxicity. A research pathway to effective therapy of receptor-mediated autoimmune diseases, which probably include the psychoses, is now apparent. It involves finding the autoantibodies, then cloning of their antigenic targets, as has been done for Graves' disease. This will provide knowledge of the peptide sequences necessary for constructing therapeutic agents for selectively destroying the pathogenic forbidden clones. Meanwhile, usage of short-term therapy with prednisone could be helpful in the management of schizophrenia and should be explored.
精神分裂症及其他精神病的病因尚未明确。基于遗传及其他证据的奈特模型提出，精神分裂症是一种自身免疫性疾病，由分泌自身抗体的B淋巴细胞禁忌克隆的发展所致，这些自身抗体意外刺激某些神经元上的细胞表面受体，影响大脑边缘系统。一名患有格雷夫斯病的毛利男子出现了一种异常缺陷，使他对通常有效的抗甲状腺药物无反应，于是给他使用了泼尼松（一种非特异性免疫抑制剂）进行治疗。这一治疗非常成功，随着甲状腺激素水平和甲状腺大小的降低，致病的促甲状腺自身抗体的血液水平也降低了。不幸的是，由于类固醇毒性，高剂量泼尼松只能使用一个月。现在，一条针对受体介导的自身免疫性疾病（可能包括精神病）的有效治疗研究途径已经明晰。它包括找到自身抗体，然后克隆其抗原靶点，就像在格雷夫斯病中所做的那样。这将提供构建用于选择性破坏致病性禁忌克隆的治疗药物所需的肽序列知识。同时，短期使用泼尼松治疗可能有助于精神分裂症的管理，应该对此进行探索。
