Salvi M, Fukazawa H, Bernard N, Hiromatsu Y, How J, Wall J R
Thyroid Research Unit, McGill University, Montreal General Hospital Research Institute, Quebec, Canada.
Endocr Rev. 1988 Nov;9(4):450-66. doi: 10.1210/edrv-9-4-450.
This review has focused on the nature and significance of aAB detected in the serum of patients with EAD. Although many antibodies are characteristically detected in the serum of patients with such disorders, only a few are of known pathogenic significance. Antibodies that react with soluble cytoplasmic antigens are not expected to be harmful. On the other hand, membrane or cell surface-directed antibodies are likely to be damaging, either by lysis of the cell membrane, or by reaction with hormone or other surface receptors. Clinically, measurement of aAB has important diagnostic and management value. Moreover, detection of certain antibodies before the onset of disease raises hope that the corresponding disorders may be preventable, e.g. by specific immunosuppression of those subjects, or patients, with positive tests. The possible role of aAB in the association of organ-specific AID by cross-reacting with shared epitopes in various tissues has been highlighted by the recent finding, from the authors' laboratory, of antibodies reactive with a 64-kDa membrane protein found in several tissues, including thyroid, eye muscle, and pancreas, which are frequent sites for autoimmune inflammation. Study of such antibodies and the molecular characterization of the corresponding antigens in the various involved tissues should provide information concerning the role of cross-reactivity in autoimmunity as well as leading to the development of specific immunotherapeutic agents.
本综述聚焦于在伴有眼肌麻痹的急性脱髓鞘性多发性神经炎(EAD)患者血清中检测到的自身抗体(aAB)的性质及意义。尽管在患有此类疾病的患者血清中可特征性地检测到多种抗体,但只有少数具有已知的致病意义。与可溶性细胞质抗原发生反应的抗体预计不会有害。另一方面,针对膜或细胞表面的抗体可能具有破坏性,其机制要么是通过细胞膜裂解,要么是通过与激素或其他表面受体发生反应。在临床上,aAB的检测具有重要的诊断和管理价值。此外,在疾病发作前检测到某些抗体,这让人们燃起希望,即相应的疾病或许是可以预防的,例如通过对检测呈阳性的个体或患者进行特异性免疫抑制。作者实验室最近的一项发现突出了aAB通过与各种组织中的共同表位发生交叉反应,在器官特异性自身免疫性疾病(AID)关联中可能发挥的作用。该发现表明,在包括甲状腺、眼肌和胰腺等自身免疫性炎症常见部位的几种组织中,均发现了与一种64 kDa膜蛋白发生反应的抗体。对这些抗体以及各种受累组织中相应抗原的分子特征进行研究,应能提供有关交叉反应在自身免疫中作用的信息,并有助于开发特异性免疫治疗药物。