Concentration of Insulin Autoantibodies at Onset of Type I Diabetes: Inverse Log-Linear Correlation With Age

Vardi, Pnina; Ziegler, AG; Jh, Mathews; Dib, Sarah; Rj, Keller; At, Ricker; Ji, Wolfsdorf; Rd, Herskowitz; Rabizadeh, A; Gs, Eisenbarth

doi:10.2337/diacare.11.9.736

Cited by 184 publications

(111 citation statements)

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“…In particular, IAA are an important predictor in the diagnosis of T1D (3). IAA are frequently found and are among the first detectable autoantibodies in young children developing the disease (12)(13)(14)(15)(16). They precede T1D with reported appearance between 8 and 20 wk of age in the NOD mouse and they correlate with diabetes incidence (3).…”

Section: Iaa As An Early Phenotypic Marker For T1dmentioning

confidence: 99%

Early and Quantal (by Litter) Expression of Insulin Autoantibodies in the Nonobese Diabetic Mice Predict Early Diabetes Onset

Melanitou

Devendra

Liu

et al. 2004

The Journal of Immunology

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International audienceAiming to study the early stages of type 1 diabetes phenotype, before insulitis appears, we measured insulin autoantibodies (IAA) between 3 and 5 wk of age in the NOD mouse (early-IAA (E-IAA)). We report that IAA are found as early as at 3 wk of age, at weaning, and their expression is a quantal phenotype. Maternal autoantibody status influences this early phenotype, because animals of litters issued from IAA-positive ante partum mothers develop E-IAA with a significantly higher incidence than animals issued from IAA-negative mothers. These E-IAA represent synthesized rather than transplacental autoantibodies, as evidenced by higher levels in many offspring compared with maternal IAA, and negative as well as positive offspring in the same litters and it correlates with early diabetes onset, defining the first autoimmune window in diabetes pathogenesis. Therefore, autoimmune processes leading to type 1 diabetes initiate early in life, are influenced by maternal autoantibody status, and can be revealed by the presence of IAA. Our data suggest that the mechanisms responsible for the breakdown of self-tolerance are subjected not only to genetic predisposition, but also to the physiological status of the mother. Pathological progression to autoimmunity is marked by the presence of immunological windows relating early steps with final disease onset

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Section: Iaa As An Early Phenotypic Marker For T1dmentioning

confidence: 99%

Early and Quantal (by Litter) Expression of Insulin Autoantibodies in the Nonobese Diabetic Mice Predict Early Diabetes Onset

Melanitou

Devendra

Liu

et al. 2004

The Journal of Immunology

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“…IAA are important in the prediction of type 1 diabetes, especially in young children, as their level and prevalence at diagnosis correlate inversely with age [2,3]. Measurement of IAA was initially limited by the high serum volume required for the early immunoprecipitation assays, which used polyethylene glycol to separate immune complexes [4].…”

Section: Introductionmentioning

confidence: 99%

Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies

Schlosser

Mueller

Törn³

et al. 2010

Diabetologia

151

125

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Aims/hypothesis Insulin autoantibodies (IAA) are important in type 1 diabetes risk assessment. However, their determination varies more between laboratories than other diabetes autoantibodies. The Diabetes Antibody Standardization Program (DASP) aims to improve and standardise measurement of autoantibodies associated with type 1 diabetes. We report the results of measurement of IAA from DASP workshops in 2002, 2003 and 2005. Methods Up to 32 laboratories in 14 countries participated in each workshop. Aliquots of coded sera from 50 patients with newly diagnosed type 1 diabetes and 100 blood donor controls were circulated to participating laboratories. Reported results were analysed using receiver operator characteristic (ROC) curves. We compared concordance of antibody levels by ranking, IAA and insulin antibody ( There was, however, marked variation between assays. The range of AUC was 0.36-0.91 and that of laboratory-assigned sensitivity was 22-57%. Concordance of ranking of patient serum samples was related to AUC (p<0.001). Using an index related to common IAA and IA-positive or -negative control sera improved the concordance between assays (p<0.0001). Conclusions/interpretation The overall performance of IAA assays has improved but there is still wide variation between laboratories. Concordance between assays would be improved by the use of a common reference reagent.Keywords Adjusted sensitivity . AUC . Insulin autoantibodies . Insulin autoantibody index . Islet autoantibodies . Prediction . Reference serum . Sensitivity . Specificity Abbreviations AS95Sensitivity adjusted to 95% specificity CDC Centers for Disease Control and PreventionElectronic supplementary material The online version of this article

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“…UK Prospective Diabetes Study (UKPDS) analyses [4] showed that, by 6 years from diagnosis of presumed type 2 diabetes, 38% of subjects requiring insulin were GADA-positive, whereas 95% of those not requiring insulin were GADA-negative. IAA, which are a frequent marker of childhood diabetes, with a frequency inversely related to age [6], are unlikely to be useful for LADA screening.…”

Section: Introductionmentioning

confidence: 99%

IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71)

et al. 2005

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Aims/hypothesis: Established autoimmune markers of type 1 diabetes, including islet cell autoantibodies (ICA) and autoantibodies to glutamic acid decarboxylase (GADA) have been used to screen people presenting with type 2 diabetes for latent autoimmune diabetes in adults. We have examined the prevalence of autoantibodies to protein tyrosine phosphatase isoforms IA-2 (IA-2A) and IA-2β/phogrin (IA-2βA) in a cohort of adult UKPDS patients thought to have type 2 diabetes, and investigated the possible role of these autoantibodies in predicting requirement for insulin therapy. Methods: IA-2A and IA-2βA were measured by a validated radioimmunoassay with human recombinant autoantigens in 4,169 white Caucasian patients aged 25-65 years and newly diagnosed with type 2 diabetes. The clinical requirement for insulin therapy within 6 years was examined in 2,556 patients not randomised to insulin. Results: IA-2A and IA-2βA were present in 2.2 and 1.4%, respectively, of these patients. IA-2A were more prevalent in younger patients (p for trend <0.00001), more often associated with the HLA-DR4 allele (26.3 vs 8.0%, p<0.0001), and their presence increased the likelihood of insulin therapy requirement within 6 years from diagnosis [relative risk (95%CI) 12.2 (9.8-15.3)]. The presence of IA-2A together with GADA increased the relative risk of requiring insulin therapy from 5.4 (4.1-7.1) for GADA alone to 8.3 (3.7-18.8) and the corresponding positive predictive value from 33 to 50%. Conclusions/interpretation: In type 2 diabetes, the presence of IA-2A is infrequent, associated with the HLA-DR4 haplotype, and highly predictive of future need for insulin therapy. The measurement of IA-2βA does not provide additional information.

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Concentration of Insulin Autoantibodies at Onset of Type I Diabetes: Inverse Log-Linear Correlation With Age

Cited by 184 publications

References 0 publications

Early and Quantal (by Litter) Expression of Insulin Autoantibodies in the Nonobese Diabetic Mice Predict Early Diabetes Onset

Early and Quantal (by Litter) Expression of Insulin Autoantibodies in the Nonobese Diabetic Mice Predict Early Diabetes Onset

Diabetes Antibody Standardization Program: evaluation of assays for insulin autoantibodies

IA-2 antibody prevalence and risk assessment of early insulin requirement in subjects presenting with type 2 diabetes (UKPDS 71)

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