Organ-specific autoantibodies in children with common endocrine diseases

Bright, George M.; Blizzard, Robert M.; Kaiser, Donald L.; Clarke, William L.

doi:10.1016/s0022-3476(82)80227-8

Cited by 123 publications

(68 citation statements)

References 36 publications

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“…In our antibody-positive patients the duration of diabetes varied between 0.25 and 10 years. Another study found a higher prevalence in patients with duration of diabetes more than 10 years, but also found an overall higher prevalence of 30% (22). Previous studies reported that Tab are more frequent among girls than boys (1, 21, 22), while we and others (3, 7) did not find such a difference.…”

Section: Discussioncontrasting

confidence: 60%

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus

Hansen

Bennedbæk²,

Hansen³

et al. 1999

European Journal of Endocrinology

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Objective: An association between insulin-dependent diabetes mellitus (IDDM) and autoimmune thyroid disease is well recognized. We have studied the prevalence of thyroid dysfunction, autoimmunity and morphological abnormalities by ultrasonography in young diabetics. Subjects and methods: Among young IDDM patients less than 18 years old and living in the county of Funen, Denmark, 105 of 116 eligible patients participated. They were compared with 105 healthy children matched for sex and age. Routine thyroid function parameters (thyroxine (T 4 ), tri-iodothyronine (T 3 ), T 3 resin uptake and TSH) and thyroid autoantibodies (anti-thyroid peroxidase, TPOab, and thyroglobulin antibodies, Tgab) were measured. Thyroid size and morphology were determined by ultrasonography. Results: Two of the diabetics had previously diagnosed hypothyroidism and three new cases of subclinical hypothyroidism were found.

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Section: Discussioncontrasting

confidence: 60%

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus

Hansen

Bennedbæk²,

Hansen³

et al. 1999

European Journal of Endocrinology

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“…The relationship between certain chromosomal abnormalities (especially Down syndrome and Turner's Syndrome) and thyroid autoimmunity has been reviewed by Bright et al (1982). There are several hypotheses that attempt to describe this association; (i) chromosomal abnormalities may result in secondary autoimmune disease (ii) pre-existing autoantibodies in the mother may predispose to a chromosomal abnormality in the child (iii) both aneuploidy and autoimmune disease may be a result of another (unknown) process.…”

Section: Immunological Aspectsmentioning

confidence: 99%

Down Syndrome and Thyroid Disorders: A Review

Prasher¹

1999

Downs Syndr. Res. Pract.

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Thyroid disorders are common in the Down syndrome population but many specific areas of importance remain to be resolved. A detailed review of previously published case reports and research studies highlighting the clinical association between Down syndrome and thyroid disorders was undertaken. Historical, epidemiological, immunological, diagnostic and treatment issues are addressed. Recommendations for future management and research are considered.

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“…Conversely, 2.3% of children with AITD have islet cell antibodies compared with 0% of controls (8). Although the exact mechanisms of this association are still evolving, there is growing evidence that genetic factors play a major role (9).…”

mentioning

confidence: 99%

Shared molecular amino acid signature in the HLA-DR peptide binding pocket predisposes to both autoimmune diabetes and thyroiditis

Menconi¹,

Osman

Monti

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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There is strong genetic association between type 1A diabetes (T1D) and autoimmune thyroid disease (AITD). T1D and AITD frequently occur together in the same individual, a condition classified as a variant of the autoimmune polyglandular syndrome type 3 (APS3). Because T1D and AITD are individually strongly associated with different HLA class II sequences, we asked which HLA class II pocket sequence and structure confer joint susceptibility to both T1D and AITD in the same individual (APS3v). We sequenced the HLA-DR gene in 105 APS3v patients and 153 controls, and identified a pocket amino acid signature, DRβ-Tyr-26, DRβ-Leu-67, DRβ-Lys-71, and DRβ-Arg-74, that was strongly associated with APS3v (P = 5.4 × 10 −14 , odds ratio = 8.38). Logistic regression analysis demonstrated that DRβ-Leu-67 (P = 9.4 × 10 −13) and DRβ-Arg-74 (P = 1.21 × 10 −13 ) gave strong independent effects on disease susceptibility. Structural modeling studies demonstrated that pocket 4 was critical for the development of T1D+AITD; all disease-associated amino acids were linked to areas of the pocket that interact directly with the peptide and, therefore, influence peptide binding. The disease-susceptible HLA-DR pocket was more positively charged (Lys-71, Arg-74) compared with the protective pocket (Ala-71, Gln-74). We conclude that a specific pocket amino acid signature confers joint susceptibility to T1D+AITD in the same individual by causing significant structural changes in the MHC II peptide binding pocket and influencing peptide binding and presentation. Moreover, Arg-74 is a major amino acid position for the development of several autoimmune diseases. These findings suggest that blocking the critical Arg-74 pocket might offer a method for treating certain autoimmune conditions. autoimmunity | gene | structure T ype 1A (autoimmune) diabetes mellitus (T1D) and autoimmune thyroid disease (AITD) are the most common autoimmune endocrine disorders (1-3). Despite affecting different tissues, T1D and AITD share a common etiology. Both are organspecific autoimmune diseases characterized by infiltration of the gland by autoreactive T and B cells and production of antibodies directed at the target organs (the pancreatic islets in T1D and the thyroid in AITD), resulting in their dysfunction or destruction. In fact, there is a well-known strong association between T1D and AITD (reviewed in ref. 1). They frequently occur within the same family (aggregation) and in the same individual (comorbidity) (1). When T1D and AITD occur in the same individual the phenotype is considered, according to a commonly accepted classification, as a variant of the autoimmune polyglandular syndrome type 3 (APS3) (4,5) [in this manuscript, we use the nomenclature which defines APS3 as AITD + another autoimmune condition excluding Addison's disease (4) for better clarity, and we refer to the combination AITD+T1D in the same individual as APS3 variant (APS3v) to emphasize that this is not the only form of APS3]. However, it should be noted that the classification of APS is...

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Organ-specific autoantibodies in children with common endocrine diseases

Cited by 123 publications

References 36 publications

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus

Thyroid function, morphology and autoimmunity in young patients with insulin-dependent diabetes mellitus

Down Syndrome and Thyroid Disorders: A Review

Shared molecular amino acid signature in the HLA-DR peptide binding pocket predisposes to both autoimmune diabetes and thyroiditis

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