Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA.
J Autoimmun. 2011 Sep;37(2):79-87. doi: 10.1016/j.jaut.2011.05.005. Epub 2011 Jun 16.
Stiff Person Syndrome (SPS) is a rare autoimmune neurological disease attributable to autoantibodies to glutamic acid decarboxylase (anti-GAD) more usually associated with the islet beta cell destruction of autoimmune type 1 diabetes (T1D). SPS is characterized by interference in neurons with the synthesis/activity of the inhibitory neurotransmitter gamma amino butyric acid (GABA) resulting in the prototypic progressive spasmodic muscular rigidity of SPS, or diverse neurological syndromes, cerebellar ataxia, intractable epilepsy, myoclonus and several others. Remarkably, a single autoantibody, anti-GAD, can be common to widely different disease expressions, i.e. T1D and SPS. One explanation for these data is the differences in epitope engagement between the anti-GAD reactivity in SPS and T1D: in both diseases, anti-GAD antibody reactivity is predominantly to a conformational epitope region in the PLP- and C-terminal domains of the 65 kDa isoform but, additionally in SPS, there is reactivity to conformational epitope(s) on GAD67, and short linear epitopes in the C-terminal region and at the N-terminus of GAD65. Another explanation for disease expressions in SPS includes ready access of anti-GAD to antigen sites due to immune responsiveness within the CNS itself according to intrathecal anti-GAD-specific B cells and autoantibody. Closer study of the mysterious stiff-person syndrome should enhance the understanding of this disease itself, and autoimmunity in general.
僵人综合征（SPS）是一种罕见的自身免疫性神经系统疾病，归因于谷氨酸脱羧酶（anti-GAD）自身抗体，这些自身抗体通常与胰岛β细胞破坏的自身免疫性 1 型糖尿病（T1D）有关。SPS 的特征是神经元中抑制性神经递质γ-氨基丁酸（GABA）的合成/活性受到干扰，导致 SPS 的典型进行性痉挛性肌肉僵硬，或多种神经系统综合征、小脑共济失调、难治性癫痫、肌阵挛等。值得注意的是，单一自身抗体，即抗-GAD，可与广泛不同的疾病表现有关，即 T1D 和 SPS。这些数据的一个解释是 SPS 和 T1D 中抗-GAD 反应性的表位结合差异：在这两种疾病中，抗-GAD 抗体反应性主要针对 PLP 和 65 kDa 同工型 C 末端结构域中的构象表位区域，但在 SPS 中，还存在对 GAD67 上的构象表位（多个）以及 C 末端区域和 GAD65 N 末端的短线性表位的反应性。SPS 中疾病表现的另一个解释包括由于中枢神经系统自身的免疫反应性，抗-GAD 可轻易地进入抗原部位，根据鞘内抗-GAD 特异性 B 细胞和自身抗体。对神秘的僵人综合征的更深入研究应该会增强对这种疾病本身以及一般自身免疫性的理解。
