Urriola Nicolás, Adelstein Stephen
Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Sydney, Australia; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia; Central Sydney Immunopathology Laboratory, NSW Health Pathology, Australia.
Autoimmun Rev. 2022 Feb;21(2):102988. doi: 10.1016/j.autrev.2021.102988. Epub 2021 Oct 30.
Autoimmune Autonomic Ganglionopathy (AAG) is a rare immune-mediated disease of the autonomic nervous system. The incidence of AAG is unknown and diagnosis is often difficult due to the multicompartmental nature of the autonomic nervous system - sympathetic, parasympathetic and enteric components - with variable severity and number of components affected. Diagnostic confidence is increased when ganglionic acetylcholine receptor (gnACHR) autoantibodies are detected. Three gnACHR autoantibody diagnostic assays have been described (two binding assays, one receptor immunomodulation assay), but cross-validation between assays is limited. The prevalence of gnACHR autoantibodies in AAG is not known, with application of different clinical and laboratory criteria in the few studies of AAG cohorts and large retrospective laboratory studies of positive gnACHR autoantibodies lacking adequate clinical characterisation. Furthermore, the rate of unexpected gnACHR autoantibody positivity in conditions without overt autonomic dysfunction (false positive results) adds to the complexity of their interpretation. We review the pathophysiology of gnACHR autoantibodies and assays for their detection, with immunomodulation and high titer radioimmunoprecipitation results likely offering better AAG disease identification.
自身免疫性自主神经节病（AAG）是一种罕见的自主神经系统免疫介导疾病。AAG的发病率尚不清楚，由于自主神经系统的多部分性质（交感神经、副交感神经和肠神经系统成分），且受影响的成分严重程度和数量各不相同，诊断往往很困难。检测到神经节乙酰胆碱受体（gnACHR）自身抗体时，诊断的可信度会提高。已经描述了三种gnACHR自身抗体诊断检测方法（两种结合检测方法，一种受体免疫调节检测方法），但检测方法之间的交叉验证有限。AAG中gnACHR自身抗体的患病率尚不清楚，在少数AAG队列研究以及对gnACHR自身抗体阳性的大型回顾性实验室研究中，应用了不同的临床和实验室标准，且缺乏充分的临床特征描述。此外，在没有明显自主神经功能障碍（假阳性结果）的情况下，gnACHR自身抗体意外阳性的发生率增加了对其结果解释的复杂性。我们综述了gnACHR自身抗体的病理生理学及其检测方法，免疫调节和高滴度放射免疫沉淀结果可能为AAG疾病的识别提供更好的依据。
