Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland.
Diabetes Metab Res Rev. 2010 May;26(4):271-9. doi: 10.1002/dmrr.1083.
Glutamic acid decarboxylase (GAD) is a rate-limiting enzyme in the synthesis of gamma-amino butyric acid (GABA) and an important autoantigen both in patients with type 1 diabetes (T1D) and stiff-person syndrome (SPS). Autoantibodies (GADA) to the 65-kDa isoform of GAD are a characteristic feature in both diseases. Approximately 30% of patients with SPS develop diabetes, yet, it is unclear to which extent co-existing autoimmunity to GAD65 and other islet autoantigens determines the risk of developing T1D.
In this study, we monitored CD4+ T-cell responses to GAD65 and proinsulin in a patient with SPS who remained normoglycaemic during the 46-month follow-up.
Fluctuating but persistent T-cell reactivity to GAD65 was identified, as well as T-cell reactivity to proinsulin at one time point. The majority of the T-cell clones isolated from the patient with SPS produced high levels of Th2 cytokines (IL-13, IL-5 and IL-4). We also examined levels of GADA, insulin and IA-2 autoantibodies, and epitope specificity of GADA. In both serum and cerebrospinal fluid (CSF), GADA levels were high, and GADA persisted throughout the follow-up. Despite T-cell reactivity to both GAD65 and proinsulin, autoantibodies to other islet autoantigens did not develop.
Further follow-up will determine whether the beta-cell autoimmunity observed in this patient will eventually lead to T1D.
谷氨酸脱羧酶（GAD）是γ-氨基丁酸（GABA）合成的限速酶，是 1 型糖尿病（T1D）和僵人综合征（SPS）患者的重要自身抗原。针对 GAD 的 65kDa 同工型的自身抗体（GADA）是这两种疾病的特征。大约 30%的 SPS 患者会发展为糖尿病，但尚不清楚同时存在针对 GAD65 和其他胰岛自身抗原的自身免疫会在何种程度上决定发生 T1D 的风险。
在这项研究中，我们监测了一位 SPS 患者在 46 个月的随访期间保持血糖正常时对 GAD65 和胰岛素原的 CD4+T 细胞反应。
发现了对 GAD65 的波动但持续的 T 细胞反应，以及在一个时间点对胰岛素原的 T 细胞反应。从 SPS 患者中分离出的大多数 T 细胞克隆产生高水平的 Th2 细胞因子（IL-13、IL-5 和 IL-4）。我们还检查了 GADA、胰岛素和 IA-2 自身抗体的水平以及 GADA 的表位特异性。在血清和脑脊液（CSF）中，GADA 水平均较高，并且在整个随访过程中均持续存在。尽管对 GAD65 和胰岛素原均有 T 细胞反应，但其他胰岛自身抗体并未产生。
进一步的随访将确定该患者观察到的β细胞自身免疫是否最终会导致 T1D。
