Crisp Sarah J, Balint Bettina, Vincent Angela
aInstitute of Neurology, University College London, London, UK bDepartment of Neurology, University Hospital Heidelberg, Germany cNuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
Curr Opin Neurol. 2017 Jun;30(3):310-316. doi: 10.1097/WCO.0000000000000450.
This review highlights the recent discovery of antibodies to glycine receptor (GlyR-Ab) and discusses the relationship between these antibodies and neurological disorders.
Since the initial description in 2008 of antibodies to glycine receptors (GlyR-Abs) in a patient with progressive encephalomyelitis with rigidity and myoclonus (PERM), these antibodies have been found in PERM and in some patients with a variety of stiff person spectrum (SPS) or related disorders. Patients with GlyR-Abs often improve with aggressive immunotherapy, and antibody titres correlate with disease severity. Around 25% of patients have another autoimmune condition and 10-20% have an underlying malignancy. GlyR-Abs bind to extracellular determinants, are mainly Immunoglobulin G1 subclass and induce GlyR internalization in Human embryonic kidney 293 cells, suggesting pathogenicity. The spectrum of neurological disease associated with GlyR-Abs has not been fully characterized, and lower titres may not be syndrome specific, but GlyR-Abs, like antibodies to other neuronal cell-surface antigens, define immunotherapy-responsive disease and are likely to be pathogenic. This distinguishes them from the glutamic acid decarboxylase antibodies that can also be found at high titres in patients with classical stiff person syndrome which is more often chronic and relatively resistant to immunological treatments.
Irrespective of the clinical features, GlyR-Abs are helpful in the diagnosis of patients who very often have a subacute, progressive and life-threatening disorder which shows a favourable response to immunotherapy.
本综述重点介绍了甘氨酸受体抗体（GlyR-Ab）的最新发现，并讨论了这些抗体与神经系统疾病之间的关系。
自2008年首次描述一名患有进行性脑脊髓炎伴僵硬和肌阵挛（PERM）的患者体内存在甘氨酸受体抗体（GlyR-Abs）以来，这些抗体已在PERM患者以及一些患有各种僵人谱系障碍（SPS）或相关疾病的患者中被发现。GlyR-Abs患者通常通过积极的免疫治疗会有所改善，并且抗体滴度与疾病严重程度相关。约25%的患者患有另一种自身免疫性疾病，10-20%的患者患有潜在恶性肿瘤。GlyR-Abs与细胞外决定簇结合，主要为免疫球蛋白G1亚类，并在人胚肾293细胞中诱导GlyR内化，提示其致病性。与GlyR-Abs相关的神经系统疾病谱尚未完全明确，较低的滴度可能不具有综合征特异性，但GlyR-Abs与其他神经元细胞表面抗原的抗体一样，可定义对免疫治疗有反应的疾病，并且可能具有致病性。这使其与谷氨酸脱羧酶抗体不同，后者在经典僵人综合征患者中也可能高滴度存在，而经典僵人综合征通常更具慢性且对免疫治疗相对耐药。
无论临床特征如何，GlyR-Abs有助于诊断那些常患有亚急性、进行性且危及生命的疾病且对免疫治疗有良好反应的患者。
