Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents

Jonsdottir, Berglind; Andersson, Cecilia; Carlsson, Annelie; Delli, Ahmed J.; Forsander, Gun; Ludvigsson, Johnny; Marcus, Claude; Samuelsson, Ulf; Örtqvist, Eva; Lernmark, Åke; Ivarsson, Sten-Anders; Larsson, Helena Elding

doi:10.1007/s00125-013-2934-9

Cited by 39 publications

(38 citation statements)

References 40 publications

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“…Additionally, it has long been recognized that positive AchRAb is synonymous with the onset of OMG [36]. Furthermore, as to HLA-DQ polymorphism, a result consistent with ours has also been reported by Jonsdottir et al [37] that HLA-DQ is associated with positive T-Ab, further supporting our findings. However, despite the discovery of correlation between HLA-DQ and positive T-Ab in patients with TAO-combined OMG, we failed to figure out the mechanism behind it, which awaits further studies to elucidate it.…”

Section: Discussionsupporting

confidence: 93%

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy

et al. 2017

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The present study aims to explore the correlation of human leucocyte antigen (HLA)-DQ and tumour necrosis factor (TNF)-α gene polymorphisms with ocular myasthenia gravis (OMG) combined with thyroid-associated ophthalmopathy (TAO). From March 2009 to March 2015, 56 OMG patients complicated with TAO (OMG + TAO group), 134 patients diagnosed with OMG only (OMG group) and 236 healthy individuals (control group) were enrolled in the present study. PCR-sequence specific primer (PCR-SSP) was used for HLA-DQ genotyping and PCR-restriction fragment length polymorphism (PCR-RFLP) for TNF-α genotyping. ELISA kit was applied to detect acetylcholine receptor antibody (AchRAb) level and chemiluminescence immunoassay (CLIA) to measure thyroid-associated antibody (T-Ab) level. Logistic regression analysis was carried out to analyse the risk factors for OMG combined with TAO. DQA1*0103 showed lower frequency in the OMG group than in the control group. DQA1*0301 showed increased and DQB1*0601 showed decreased frequency in the OMG + TAO group. DQB1*0501 showed higher frequency in the OMG and OMG + TAO groups than in the control group. Patients carrying TNF-α -863C > A (CA + AA) might confront with greater risks of OMG combined with TAO. Frequency of DQA1*0103/*0301 and DQB1*0501/*0601, and TNF-α -863C > A, -238G > A and -308G > A were associated with the levels of AchRAb and T-Ab. TNF-α -863C > A (CA + AA) and high level of T-Ab were risk factors for OMG combined with TAO. Our results demonstrate that TNF-α -863 polymorphism is possibly correlated with the risk of OMG combined with TAO.

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Section: Discussionsupporting

confidence: 93%

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy

et al. 2017

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“…To our knowledge, this is the first study to prove that a strong relationship exists between the presence of these two autoantibodies (ZnT8A and ATPO) in newly diagnosed diabetic adult patients. Independently, in a large population of children with new onset of T1DM, Jonsdottir et al (29) discovered that both types of thyroid autoantibodies (ATPO and anti-thyroglobulin antibodyATg) were associated with GADA and ZnT8A. Zinc modulates the expression of many genes within the immune cells and is an essential element for immune function.…”

Section: Discussionmentioning

confidence: 99%

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Rogowicz-Frontczak

Zozulińska‐Ziółkiewicz

Litwinowicz

et al. 2014

European Journal of Endocrinology

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Objective: The diagnosis of autoimmune diabetes in non-obese adults is based on the detection of glutamic acid decarboxylase autoantibodies (GADA), islet cell antibodies (ICA) and antibodies to tyrosine phosphatase (IA-2A). Zinc transporter 8 (ZnT8) has been identified as a new autoantigen in patients with type 1 diabetes mellitus. The coincidence of autoimmune thyroiditis (AITD) with diabetes is common; therefore, screening of TSH and thyroid peroxidase antibodies (ATPO) is recommended during the diagnosis of diabetes. In this study, we determined whether the occurrence of islet autoantibodies is associated with a positive titre of ATPO in newly diagnosed adult-onset autoimmune diabetic patients. Results: In the study population, 70% (nZ56) of the subjects were positive for at least one of the four assessed markers of autoimmune diabetes (83.9% GADA, 62.5% ICA, 42.8% IA-2A and 33% ZnT8A) and 37.5% of the subjects were positive for ATPO. The ZnT8A-positive subjects had higher ATPO titres than the ZnT8A-negative subjects (172.7 (IQR: 0.36-410.4) vs 92.4 (IQR: 0-23.7) IU/ml, PZ0.001). Based on the assessed islet autoantibodies, the occurrence of positive ZnT8A and GADA was found to be related to a positive titre of ATPO using logistic regression (ORZ5.48, 95% CI: 1.65-18.14, PZ0.006 and ORZ3.42, 95% CI: 1.09-10.71, PZ0.03 respectively). Conclusions: In non-obese adults with new-onset diabetes, the presence of GADA and especially ZnT8 autoantibodies increases the risk of AITD.

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“…Furthermore, there is heterogeneity in the natural history of AITD in patients with type 1 diabetes: AITD may be diagnosed either at diabetes onset or during the follow-up, and the measurement of TPOAb and TGAb is useful to predict the development of future AITD. We and others have previously reported the association between anti-thyroid autoimmunity and antiislet autoantibodies, especially glutamic acid decarboxylase 65 autoantibodies (GAD65A) and zinc transporter 8 autoantibodies (ZnT8A) [4][5][6][7] . The levels and the prevalence of GAD65A are higher and more persistent in type 1 diabetic patients with AITD compared to type 1 diabetes alone [4] .…”

Section: Introductionmentioning

confidence: 99%

Sequential elevation of autoantibodies to thyroglobulin and glutamic acid decarboxylase in type 1 diabetes

Kawasaki¹,

Yasui²,

Tsurumaru³

et al. 2013

WJD

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We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies (GAD65A) in patients with type 1 diabetes and autoimmune thyroid disease. Here we describe a 32-year-old Japanese female with a thirteen-year history of type 1 diabetes whose levels of GAD65A were elevated just after the emergence of anti-thyroid autoimmunity. At 19 years of age, she developed diabetic ketoacidosis and was diagnosed with type 1 diabetes. She had GAD65A, insulinoma-associated antigen-2 autoantibodies (IA-2A), and zinc transporter-8 autoantibodies (ZnT8A), but was negative for antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TGAb) at disease onset. ZnT8A and IA-2A turned negative 2-3 years after the onset, whereas GAD65A were persistently positive at lower level (approximately 40 U/mL). However, just after the emergence of TGAb at disease duration of 12.5 years, GAD65A levels were reelevated up to 5717 U/mL in the absence of ZnT8A and IA-2A. Her thyroid function was normal and TPOAb were consistently negative. She has a HLA-DRB1*03:01/*04:01-DQB1*02:01/*03:02 genotype. Persistent positivity for GAD65A might be associated with increased risk to develop anti-thyroid autoimmunity.© 2013 Baishideng. All rights reserved.Key words: Autoimmune thyroid disease; Case report; Glutamic acid decarboxylase autoantibodies; Type 1 diabetes Core tip: This paper describes a case of type 1 diabetes whose levels of glutamic acid decarboxylase 65 autoantibodies (GAD65A) were reelevated just after the emergence of anti-thyroid autoimmunity at disease duration of 12.5 years without any clinical signs of thyroid dysfunction. This case report suggests that persistent positivity for GAD65A is associated with increased risk to develop anti-thyroid autoimmunity.

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Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents

Cited by 39 publications

References 40 publications

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy

Correlation of HLA-DQ and TNF-α gene polymorphisms with ocular myasthenia gravis combined with thyroid-associated ophthalmopathy

Are zinc transporter type 8 antibodies a marker of autoimmune thyroiditis in non-obese adults with new-onset diabetes?

Sequential elevation of autoantibodies to thyroglobulin and glutamic acid decarboxylase in type 1 diabetes

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