Key Laboratory of Diabetes Immunology, Ministry of Education, Diabetes Center, Metabolic Syndrome Research Center, Institute of Metabolism and Endorcrinology, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.
Acta Diabetol. 2011 Jun;48(2):149-55. doi: 10.1007/s00592-010-0250-0. Epub 2011 Jan 7.
This study aimed at determining which GAD65 epitopes the spontaneous antibodies recognized and whether the epitope-specific GAD65Abs could be associated with the development of thyroid autoimmunity in Chinese adult-onset type 1 diabetes (T1DM) and latent autoimmune diabetes in adults (LADA). The levels of GAD65Abs and their reactivities to N-terminal (GAD65-N), middle (GAD65-M) and C-terminal (GAD65-C) regions of human GAD65 were measured by radioligand assay in 109 patients with adult-onset T1DM and 107 with LADA. TPOAb, TGAb and the genotypes of HLADQA1-DQB1 were determined. The percentage of LADA patients with GAD65-NAb was significantly higher than that of adult-onset T1DM patients (21.5% vs. 11.0%, P = 0.037), but LADA patients with GAD65-CAb less than T1DM patients (47.7% vs. 70.6%, P = 0.001). LADA patients with both GAD65-M and GAD65-CAb (GAD65-M + CAb) appeared to be at higher risk for the development of thyroid autoimmunity, lower serum C-peptide level and the requirement for insulin therapy (P < 0.05). More frequent T1DM patients with HLADQA103-DQB10303 developed GAD65-M + CAb (55.8% vs. 35.1%, P = 0.008). In comparison with those without thyroid autoimmunity, more frequent T1DM patients and LADA patients with thyroid autoimmunity displayed GAD65-M + CAbs (44.0% vs.16.9% and 53.1% vs. 17.3%, P = 0.002 and <0.001, respectively) with a diagnostic specificity of 83.1 or 82.7% for thyroid autoimmunity, respectively. LADA patients with GAD65-M + CAbs had clinical features similar to T1DM patients. Adult-onset T1DM and LADA patients with GAD65-M + CAbs are at an increased risk for the development of thyroid autoimmunity.
本研究旨在确定自发性抗体识别的 GAD65 表位，以及表位特异性 GAD65Abs 是否与中国成人发病 1 型糖尿病（T1DM）和成人隐匿性自身免疫性糖尿病（LADA）患者甲状腺自身免疫的发展相关。通过放射配体测定法测量了 109 例成人发病 T1DM 和 107 例 LADA 患者的 GAD65Abs 水平及其对人 GAD65 的 N 端（GAD65-N）、中（GAD65-M）和 C 端（GAD65-C）区域的反应性。测定 TPOAb、TGAb 和 HLA-DQA1-DQB1 基因型。GAD65-NAb 阳性的 LADA 患者比例明显高于成人发病 T1DM 患者（21.5%比 11.0%，P=0.037），但 GAD65-CAb 阳性的 LADA 患者比例低于 T1DM 患者（47.7%比 70.6%，P=0.001）。同时具有 GAD65-M 和 GAD65-CAb（GAD65-M+CAb）的 LADA 患者似乎更易发生甲状腺自身免疫、血清 C 肽水平更低且需要胰岛素治疗（P<0.05）。更常见的 HLA-DQA103-DQB10303 阳性 T1DM 患者出现 GAD65-M+CAb（55.8%比 35.1%，P=0.008）。与无甲状腺自身免疫的患者相比，更多的 T1DM 患者和有甲状腺自身免疫的 LADA 患者显示出 GAD65-M+CAb（44.0%比 16.9%和 53.1%比 17.3%，P=0.002 和<0.001），甲状腺自身免疫的诊断特异性分别为 83.1%和 82.7%。具有 GAD65-M+CAb 的 LADA 患者具有与 T1DM 患者相似的临床特征。具有 GAD65-M+CAb 的成人发病 1 型糖尿病和 LADA 患者发生甲状腺自身免疫的风险增加。
