Analysis of diabetes-associated autoantibodies in children and adolescents with autoimmune thyroid diseases

Rydzewska, Marta; Michalak, Justyna; Bossowska, Anna; Chen, Shu; Black, Sarah; Powell, Michael J.; Furmaniak, Jadwiga; Smith, Bernard Rees; Bossowski, Artur

doi:10.1515/jpem-2018-0367

Cited by 5 publications

(7 citation statements)

References 40 publications

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“…Out of 56 studies included in the systematic review, 25 were case‐control studies, 24‐47 17 were cohort studies 48‐64 and 14 were cross‐sectional studies 65‐78 . No clinical trials met the criteria used in the systematic review.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Botello

Herrán

Salcedo

et al. 2020

Clinical Endocrinology

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Background Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. Methods This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). Results A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case‐controls, 17 were cohorts, and 14 were cross‐sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85‐81.60). Graves’ disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23‐70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti‐proinsulin, anti‐parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72‐16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76‐24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. Conclusions Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

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Section: Resultsmentioning

confidence: 99%

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Botello

Herrán

Salcedo

et al. 2020

Clinical Endocrinology

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“…In accord with these findings, our study illustrated the prevalence of ZnT8A in non-diabetic GD or HT patients significantly higher than that in HC but lower than T1DM with AITD patients as expected, which pointed out the perspective on ZnT8A's representativeness in endocrine autoimmune diseases. Rydzewska et al 23 found that the strong ZnT8 expression could been observed in almost all of the thyroid follicular cells and some of the cytoplasm and the perinuclear area of the hyperplastic C cells. In keeping with that, ZnT8 was identified as a major autoantigen in T1DM and localized in insulin secretory granules 24,31 , which expressed in other secretory cell types of murine like pancreatic α islet cells, thyroid cubical cells and adrenal gland cortex cells as well 32 .…”

Section: Discussionmentioning

confidence: 99%

“…( 22 ) recruited 278 patients with newly diagnosed GD for detecting GADA, IA-2A, three variants of ZnT8A, and they observed that 7.6% of them were positive for ZnT8A at diagnosis. Rydzewska’s study, which consisted of 44 children with GD, 65 children with HT, 199 children with T1DM with or without AITDs and 58 control children ( 23 ), reported the overall prevalence of ZnT8A with AITD was 9.2%, with a similar prevalence of ZnT8A in both GD (9.1%) and HT (9.2%). Previous evidence has already shown that ZnT8A is widely distributed in a lot of endocrine or autoimmune disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have showed the prevalence rate of thyroid autoantibodies ranging from 3.7–35% in T1DM patients, some of which suggested the associations between thyroid autoantibodies and islet autoantibodies ( 10 , 11 , 12 , 13 , 14 ). However, little work has been done on the anti-islet autoimmune status in non-diabetic patients with AITD ( 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ). As summarized in Supplementary Table 1 (see section on supplementary materials given at the end of this article), the prevalence rates of glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated antigen 2 autoantibodies (IA-2A) and insulin autoantibodies (IAA) in patients with AITD were either slightly or significantly higher than those in healthy controls (HC), indicating the distinct value of studying islet immune status in AITD.…”

Section: Introductionmentioning

confidence: 99%

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Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody

Cai

Yan

et al. 2021

Endocrine Connections

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Objective: The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been little clinical reports based on large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves’ disease (GD), Hashimoto’s thyroiditis (HT) and T1DM patients with AITD. Methods: Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by radioimmunoassay. Results: The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P<0.05); but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P<0.0001). Conclusions: An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.

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“…In accordance with these findings, our study observed that the prevalence of ZnT8A in AITD was significantly lower than that in T1DM, but was still slightly higher or significantly higher than that in nAITD or healthy subjects. Rydzewska et al (22) held the opinion that the existence of ZnT8A in AITD patients may play an important role in the immune bystander responses towards ZnT8 protein expressed on thyroid. To further investigate that, thyroidectomy species have been collected from patients with thyroid nodular goiter and GD and dealt with Immunohistochemical staining.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Thyroid Disease Correlates to Islet Autoimmunity on Zinc Transporter 8 Autoantibody: A Cross-Section Study

Cai¹,

Yan²,

Gu³

et al. 2020

Preprint

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Background The most common coexisting organ-specific autoimmune disease in patients with Type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). Many studies have showed prevalence rate of thyroid autoantibodies range from 3.7-35% in T1DM patients, while some of them suggested the associations between thyroid autoantibodies and islet autoantibodies. However, little work has been done about the anti-islet autoimmune status in patients with autoimmune thyroid disease (AITD), and so far there have been no clinical report based on large population about zinc transporter 8 autoantibody (ZnT8A) in patients with AITD. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in AITD patients. Methods In total 740 AITD patients, 108 type 1 diabetes mellitus (T1DM) patients with AITD, 172 non-autoimmune thyroid disease (nAITD) patients and 115 healthy controls were recruited in the cross-sectional study. Islet autoantibodies, ZnT8A, GADA, IA-2A and thyroid autoantibodies, TPOAb, TGAb, TRAb were detected with Radioimmunoassay and Chemiluminescence. Islet autoantibody relative value was established to compare the distribution of the three islet autoantibodies. Results The prevalence of ZnT8A and GADA in AITD group was significantly higher than that in healthy controls (ZnT8A: 15.00% vs 1.74%, GADA: 7.97% vs 0.87%, both P<0.05). Similarly, the prevalence of IA-2A in AITD group was higher than that in healthy controls (4.19% vs 0%, P<0.05). However, any islet autoantibodies positive rate in AITD group was significantly lower than that in T1DM with AITD group. Analysis of multivariable linear regression suggested that ZnT8A relative value was positively related with GADA relative value (β=0.352, P<0.01) and TPOAb titer (β=0.002, P<0.01), and GADA relative value was also positively related with ZnT8A relative value (β=0.183, P<0.01). Conclusions An increased prevalence of ZnT8A as well as a relatively high prevalence of islet autoimmunity was found in AITD patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity. Trial registration Retrospectively registered.

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Analysis of diabetes-associated autoantibodies in children and adolescents with autoimmune thyroid diseases

Cited by 5 publications

References 40 publications

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta‐analysis

Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody

Autoimmune Thyroid Disease Correlates to Islet Autoimmunity on Zinc Transporter 8 Autoantibody: A Cross-Section Study

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