Genetics of the Autoimmune Polyglandular Syndrome Type 3 Variant

Dittmar, Manuela; Kahaly, George J.

doi:10.1089/thy.2010.1639

Cited by 73 publications

(43 citation statements)

References 61 publications

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“…Pathological changes in HPT axis and impairment of its regulation can lead to several thyroid diseases, cardiovascular, and neurological disorders [3][4][5]. Thyroid dysfunctions can manifest as complications of some diseases, including type 1 diabetes mellitus (DM1) [6][7][8]. First data showing that thyroid diseases are much more common in patients with DM1 were obtained in the early 1980s [9,10].…”

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confidence: 99%

“…First data showing that thyroid diseases are much more common in patients with DM1 were obtained in the early 1980s [9,10]. Later, it was shown that about one third of patients with DM1 have autoimmune thyroid diseases, such as Graves' disease, Hashimoto's thyroiditis, and pospartum thyroiditis [6,8]. Historically, the functional link between DM1 and dysfunctions of HPT axis and the thyroid gland was studied giving preference to experi-…”

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confidence: 99%

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The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

et al. 2015

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The functions of hypothalamic-pituitary-thyroid axis are attenuated in type 1 diabetes mellitus due to insulin deficiency. The use of intranasally administered insulin is of considerable interest for treatment of diabetes and cognitive disorders, but its effect on the thyroid system has not been investigated yet. We studied the influence of long-term treatment with intranasal insulin on the hypothalamic-pituitary-thyroid axis of nondiabetic rats and diabetic animals with streptozotocin models of acute and mild type 1 diabetes mellitus. This treatment was carried out for 28 days in acute (daily does of 0.3, 0.6, and 1.5?IU of insulin per rat) and for 135 days in mild diabetes (daily dose of 0.45?IU/rat). Nondiabetic rats were treated in a similar manner. Intranasal insulin in both models of diabetes resulted in the improvement of thyroid status; manifested as increase of thyroid hormones levels and restoration of response to thyroliberin. In acute diabetes, a daily dose of 0.6?IU/rat was the most effective. Twenty eight days treatment of nondiabetic rats with intranasal insulin at a dose of 0.3?IU/rat resulted in a significant increase of free and total thyroxine levels. Longer treatment of rats with mild diabetes and nondiabetic animals significantly increased thyrotropin level. Thus, long-term intranasal insulin treatment restored the hypothalamic-pituitary-thyroid axis function in type 1 diabetes, but led to a significant increase in the thyrotropin level, which must be considered when designing a strategy for the use of intranasal insulin in clinical applications.

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The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

et al. 2015

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“…With regard to the pathogenic mechanisms that contribute to the development of APS3v, there are several hypothetical mechanisms by which HLA could be involved in a common etiology of T1D and AITD (1,9). First, some HLA susceptibility alleles for T1D might be in tight linkage disequilibrium with that for AITD.…”

Section: Frequencies Of Antigen or Allele Controlmentioning

confidence: 99%

“…Type 1 diabetes mellitus (T1D) and autoimmune thyroid disease (AITD) are common autoimmune endocrine diseases, and the occurrence of both T1D and AITD in the same patient is defined as autoimmune polyglandular syndrome type 3 variant (APS3v) (1). Epidemiological evidence suggests that there are overlapping genetic backgrounds for APS3v (T1D and AITD).…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Occurrence of Type 1 Diabetes Mellitus and Graves' Disease: A Report of Two Cases and a Review of the Literature

et al. 2013

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Two unrelated Japanese women, 41 and 27 years of age, were admitted with histories of thirst, weight loss and palpitations of a few weeks' duration. Both were diagnosed to have diabetic ketosis or ketoacidosis with acute-onset type 1 diabetes (T1D) and Graves' disease (GD) (autoimmune polyglandular syndrome type 3 variant; APS3v), and were treated with intensive insulin therapy and anti-thyroid drugs. Human leukocyte antigen examinations showed that both cases had the HLA-A2, A24, B54, and DRB1*04:05-DQA1*03:03-DQB1*04:01 haplotype, which made them susceptible not only to APS3v, but also to both acute-onset T1D and GD. The genetic background of patients strongly contributes to the simultaneous occurrence of T1D and GD.

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“…The attack by auto-reactive T cells on the pancreas is the main immunological feature in T1DM. Deregulation of T cell homeostasis is a key event in the maintenance of self-tolerance breakdown in T1DM pathogenesis (Dittmar and Kahaly, 2010). The activation of the T cell surface receptor (TCR) triggers intracellular signaling cascades, which result in T cell activation, differentiation, and acquisition of effector function or apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Short Communication FYB polymorphisms in Brazilian patients with type I diabetes mellitus and autoimmune polyglandular syndrome type III

Addobbati¹,

Silva²,

Tavares³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to perform an association study between seven Fyn-binding protein gene (FYB)-tag single nucleotide polymorphisms (SNPs) and type I diabetes mellitus (T1DM), as well as with disease age of onset. We also assessed the role of FYB SNPs in the insurgence of autoimmune polyglandular syndrome type III (APSIII), characterized by the simultaneous presence of autoimmune thyroid disease and celiac disease, in patients with T1DM from a Northeastern Brazilian population. One hundred and seventy-seven patients with T1DM and 190 healthy individuals were genotyped for seven tag SNPs, covering most of the FYB locus, using real-time polymerase chain reaction amplification. There was no significant difference in the distribution of allele and genotype frequencies among patients and healthy individuals. Moreover, none of the tag SNPs were associated either to T1DM age of onset or to the insurgence of APSIII. However, since the FYB protein is a key component in T cell response, its gene variants might play a role in protein function, which might be testable in a population with different genetic backgrounds or by using functional assays.

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Genetics of the Autoimmune Polyglandular Syndrome Type 3 Variant

Cited by 73 publications

References 61 publications

The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

The Influence of Intranasal Insulin on Hypothalamic-Pituitary-Thyroid Axis in Normal and Diabetic Rats

Simultaneous Occurrence of Type 1 Diabetes Mellitus and Graves' Disease: A Report of Two Cases and a Review of the Literature

Short Communication FYB polymorphisms in Brazilian patients with type I diabetes mellitus and autoimmune polyglandular syndrome type III

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