title: Clinical and genetic characteristics of patients with autoimmune thyroid disease with anti-islet autoimmunity.
abstract: In contrast to the large number of studies on autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus, little is known about the anti-islet autoimmune status in patients with autoimmune thyroid diseases (AITDs). We therefore studied the anti-islet autoimmune status in patients with AITD and the clinical and genetic characteristics of AITD patients with anti-islet autoimmunity. The positivity and titer of glutamic acid decarboxylase antibody (GAD Ab) were studied in 866 Japanese patients with AITD (546 with Graves disease and 320 with Hashimoto thyroiditis), 221 patients with thyroid disease of nonautoimmune origin, and 282 control subjects. The clinical characteristics and genotypes of HLA-DRB1, DQB1, and CTLA4 were compared between AITD patients with and without GAD Ab. The prevalence of GAD Ab was significantly higher in AITD patients than in control subjects (5.8% vs 2.1%, P = .01), particularly in Graves disease (7.1% vs 2.1%, P = .0019). The prevalence of diabetes mellitus was significantly higher in AITD patients with GAD Ab than in those without (40.0% vs 10.1%, P < .0001), particularly in those with a high titer of GAD Ab (high vs low titer: 64% vs 16%, P = .001) and also in those positive for insulinoma-associated antigen 2 (IA-2) Ab (IA-2 positive vs negative: 75.0% vs 31.3%, P = .016). The AITD patients with GAD Ab were characterized by younger age at onset of diabetes, lower body mass index, higher hemoglobin A(1c) level, and higher frequency of insulin therapy than those without GAD Ab. The frequency of the DRB1*0405-DQB1*0401 haplotype was significantly higher in AITD patients with GAD Ab than in those without GAD Ab and control subjects. A single nucleotide polymorphism (rs3087243) of CTLA4 was significantly associated with AITD, but not with positivity of GAD Ab. These results indicate that patients with AITD, and in particular Graves disease, are prone to develop β-cell autoimmunity and insulin-requiring diabetes, particularly those with a high titer of GAD Ab and/or positive for both GAD and IA-2 Ab. Glutamic acid decarboxylase Ab positivity in AITD patients was associated with HLA, conferring susceptibility to type 1 diabetes mellitus.
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Kinki University School of Medicine, Osaka-sayama, Osaka 589-8511, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Moriguchi
authors.forename: Sinsuke
authors.initials: S
authors.lastname: Noso
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Harada
authors.forename: Katsumori
authors.initials: K
authors.lastname: Komaki
authors.forename: Naru
authors.initials: N
authors.lastname: Babaya
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hiromine
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Satomi
authors.initials: S
authors.lastname: Yamagata
authors.forename: Kaori
authors.initials: K
authors.lastname: Murata
authors.forename: Takahiro
authors.initials: T
authors.lastname: Higashimoto
authors.forename: Choongyong
authors.initials: C
authors.lastname: Park
authors.forename: Akinobu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ohno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006680:HLA Antigens / Q000276:immunology; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012097:Repressor Proteins / Q000032:analysis; D013967:Thyroiditis, Autoimmune / Q000150:complications / Q000235:genetics* / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D012097:Repressor Proteins; C087342:INSM1 protein, human