title: Epitope analysis of GAD65 autoantibodies in adult-onset type 1 diabetes and latent autoimmune diabetes in adults with thyroid autoimmunity.
abstract: 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 HLADQA1*03-DQB1*0303 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.
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.forename: Gan
authors.initials: G
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Shuoming
authors.initials: S
authors.lastname: Luo
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People; D001323:Autoantibodies / Q000032:analysis* / Q000097:blood / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005968:Glutamate Decarboxylase / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016036:Seroepidemiologic Studies; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000150:complications / Q000208:ethnology / Q000276:immunology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2