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

Kawasaki, Eiji; Yasui, Junichi; Tsurumaru, Masako; Takashima, Haruko; Ikeoka, Toshiyuki; Mori, Fumihiko; Akazawa, Satoru; Ueki, Ikuko; Kobayashi, Masakazu; Kuwahara, Hironaga; Abiru, Norio; Yamasaki, Hironori; Kawakami, Atsushi

doi:10.4239/wjd.v4.i5.227

Cited by 5 publications

(4 citation statements)

References 17 publications

(9 reference statements)

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“…The diagnostic sensitivity of the anti‐islet autoantibody tests we investigated tended to vary according to age at diabetes onset, with IA‐2A and ZnT8A being higher in children, and GADA being higher in adults, as reported in previous studies 6–8 . Furthermore, as previously stated, it has been reported that GADA’s persistent presence is associated with thyroid autoimmunity in patients with type 1 diabetes 9,22 and the chromosome, 3q28, in a region of strong linkage disequilibrium in the first intron of the gene, LPP 16 , which was originally identified as a susceptibility locus for celiac disease 23 and autoimmune thyroid disease 24 . Furthermore, in longitudinal studies of genetically at‐risk children followed from birth, it has been reported that the presence of multiple anti‐islet autoantibodies greatly increases the probability for type 1 diabetes 25 , and IA‐2A and ZnT8A are shown to appear later, in general, during the subclinical disease process and to herald more rapid progression to type 1 diabetes than GADA 26,27 .…”

Section: Discussionsupporting

confidence: 65%

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8

Kawasaki

Oikawa

Okada³

et al. 2020

J of Diabetes Invest

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Aims/Introduction: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes. Methods: Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8-86 years; median diabetes duration 7 years, range 0-58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran-Armitage trend test and multivariate logistic regression analysis. Results: The prevalence of IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti-islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11-30 years), the interaction was significant only for ZnT8A, and for those with late-onset diabetes (aged ≥31 years) only for IA-2A. Conclusions: The current study showed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.

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Section: Discussionsupporting

confidence: 65%

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8

Kawasaki

Oikawa

Okada³

et al. 2020

J of Diabetes Invest

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“…The dynamics of humoral autoimmunity to islet autoantigens in association with anti-thyroid autoimmunity in T1DM is not clear. More frequent occurrence of positive anti-thyroid antibodies has been reported in T1DM patients as well as in LADA subjects with higher GADA titres than in those without GADA or with lower titres (15,17,27). Kawasaki et al (27) also found that persistent positivity for GADA could be associated with an increased risk of developing anti-thyroid autoimmunity in the future.…”

Section: Discussionmentioning

confidence: 97%

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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“…Third, the diagnosis of autoimmune diseases in most cases was based on clinical manifestations, leaving the possibility that subclinical cases may be included in the non‐AID complicated patients. Given that high GADA levels have been detected in type 1 diabetes patients with subclinical autoimmune thyroid disease 16 , it would be beneficial to investigate the 3 Screen ICA levels in such cases.…”

Section: Discussionmentioning

confidence: 99%

Improving diagnostic accuracy of 3 Screen ICA ELISA kit in the identification of Japanese type 1 diabetes

Kawasaki

Jinnouchi²,

Maeda

et al. 2023

J of Diabetes Invest

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Aim/IntroductionThis study aimed to investigate the clinical utility of 3 Screen ICA ELISA in identifying immune‐mediated type 1 diabetes in Japanese subjects.MethodsWe compared the positivity of 3 Screen ICA were compared with autoantibodies against GAD, IA‐2, and ZnT8 in 638 patients with type 1 diabetes and 159 healthy control subjects.ResultsWith a cut‐off value of 20.0 index, 67.4% of acute‐onset type 1 diabetic patients, 71.8% of slowly progressive type 1 diabetic (SPIDDM) patients, and none of the fulminant type 1 diabetic patients showed 3 Screen ICA levels above this threshold. The prevalence of 3 Screen ICA was 14.2% higher in acute‐onset type 1 diabetes and 1.6% higher in SPIDDM than in GADA. 3 Screen ICA‐positive cases were found in 4.8% of cases of individual autoantibody‐negative acute‐onset type 1 diabetes and 3.8% of SPIDDM, indicating improved diagnostic sensitivity with the 3 Screen ICA. Among individual autoantibody‐negative patients, the sum of each autoantibody level was significantly lower in fulminant type 1 diabetes than in acute onset type 1 diabetes and in SPIDDM (P < 0.0001). Additionally, 84.2% of patients negative for individual autoantibodies but positive for 3 Screen ICA had a sum of individual autoantibody levels of ≥4.7 U/mL. Furthermore, 3 Screen ICA levels were significantly higher in patients with type 1 diabetes with other autoimmune diseases than in those without (P < 0.0001).ConclusionOur findings suggest that the 3 Screen ICA ELISA may be a valuable screening tool for Japanese patients with type 1 diabetes, potentially increasing the diagnostic sensitivity and accuracy beyond the existing GADA, IA‐2A, and ZnT8A tests.

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

Cited by 5 publications

References 17 publications

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8

Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma‐associated antigen‐2 and zinc transporter 8

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

Improving diagnostic accuracy of 3 Screen ICA ELISA kit in the identification of Japanese type 1 diabetes

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