The Fourth International Serum Exchange Workshop to standardize cytoplasmic islet cell antibodies

Lernmark, Åke; Molenaar, J Jaap; Beers, Wil A.M. van; Yamaguchi, Yoshihiko; Nagataki, Shigenobu; Ludvigsson, Johnny; Maclaren, Noel K.; Arnaiz‐Villena, A.; Barbosa, Jurani; deBeaufort, C.; Becker, Dorothy J.; Becker, Frank; Betterle, Corrado; Bosi, Emanuele; Bottazzo, Gian Franco; Bright, George M.; Colman, Peter G; Dawkins, Roger L.; Elliot, R. B.; Yu, Feng; Gorus, Frans; Howard, Charles F.; Jackson, Richard A.; Karjalainen, J.; Kobayashi, Takuya; Koelle, M.; Kuzuya, Hiroshi; Kwan, Jennifer; Marchal, Cécile; Dimario, Umberto; McEvoy, Robert; Palmer, Jerry P.; Reinauer, K. M.; Riley, William J.; Scherbaum, W. A.; Singh, Gyanendra; Thivolet, C.; Vialettes, B.; Ziegler, Anette‐Gabriele

doi:10.1007/bf00403293

Cited by 71 publications

(37 citation statements)

References 8 publications

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“…Antibody positive and negative samples were included in every assay to correct for inter-assay variation. The JDF ICA standard [34,35], which is also GAD65 antibody positive as verified by immunoprecipitation [2][3][4]12] was used as the GAD65 antibody positive standard. One of the 105 IDDM patients was found to be GAD67 antibody positive as verified by immunoprecipitation [12].…”

Section: Discussionmentioning

confidence: 99%

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

et al. 1994

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SummaryInsulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n = 10) and control (n = 50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p < 0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14year-old patients (n = 105), and matched, healthy control subjects (n = 157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77 % and the specificity 92 % compared with 8 % and 98 %, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89 % (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD. [Diabetologia (1994) Abbreviations: IDDM, insulin-dependent diabetes mellitus; GAD, glutamic acid decarboxylase; ROC, receiver-operating characteristic; ICA, islet cell antibodies; JDF, Juvenile Diabetes Foundation 10p11.3-p12 [7]. GAD65 shows 65 % amino acid identity with GAD67, the isoform coded for by the GAD1 gene on chromosome 2q31 [7][8][9]. The molecular cloning of full-length human islet GAD65 [7] and rat islet GAD67 [10] cDNA has made it possible to demonstrate autoreactivity in diabetes to the recombinant proteins in both eukaryotic [11,12] and bacterial [13] expression systems. GAD65 (but not GAD67) is expressed in human islets [11,14], however, variable reactivity of patient sera has been reported [12,13,[15][16][17][18][19]. GAD65 specificity of IDDM sera was first demonstrated in our immunoprecipitation assay with recombinant GAD expressed in transfected cells [12] and recently confirmed in other assays with recombinant antigens [18,20]. The use of different assay systems and species-specific GAD65 and GAD67 may explain the lower frequency of GAD67 antibodies in these compared to previous reports [13,16]. We now report the

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Section: Discussionmentioning

confidence: 99%

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

et al. 1994

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“…The assays of islet-cell antibodies (ICA), insulin autoantibodies (IAA), anti-glutamic acid decarboxylase antibodies (GADA) and anti-insulinoma-associated antigen-2 antibodies (IA-2A) are described in detail in a recent paper by Kukko et al [12]. The disease sensitivity of the ICA assay was 100% and the specificity 98% in the Fourth Immunology and Diabetes Workshop for the Standardisation of Cytoplasmic ICA [13]. The disease sensitivity of the IAA assay was 44% and the specificity 98% in the 2002 Diabetes Autoantibody Standardisation Programme (DASP) Workshop.…”

Section: Methodsmentioning

confidence: 99%

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study

et al. 2005

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Aims/hypothesis: We aimed to assess the feasibility of a dietary intervention trial with weaning to hydrolysed formula in infants at increased risk of type 1 diabetes and to study the effect of the intervention on the emergence of diabetes-associated autoantibodies in early childhood. Methods: We studied 242 newborn infants who had a first-degree relative with type 1 diabetes and carried risk-associated HLA-DQB1 alleles. After exclusive breastfeeding, the infants underwent a double-blind, randomised pilot trial of either casein hydrolysate (Nutramigen; Mead Johnson) or conventional cow's milk-based formula until the age of 6-8 months. During a mean observation period of 4.7 years, autoantibodies to insulin, anti-glutamic acid decarboxylase and insulinoma-associated antigen-2 were measured by radiobinding assays, and islet cell antibodies (ICA) by immunofluorescence. Results: The feasibility of screening and identifying a cohort of first-degree relatives with HLA-conferred disease susceptibility, enrolling them in a dietary intervention trial and following them for seroconversion to autoantibody positivity is established. The

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“…The levels of 1CA were analysed semiquantitatively using a scale from 0 to 3 (0 = negative, 1 = weakly positive, 2 = positive, 3 = strongly positive). End-point dilution titres were examined in samples from 86 diabetic children and were expressed in Juvenile Diabetes Foundation (JDF) units relative to an international reference standard [18]. Of the diabetic children 79 %, of the sibling-control children 5 % and of the population-control children 0 % were positive for ICA.…”

Section: Methodsmentioning

confidence: 99%

Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children

et al. 1994

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Summary Associations of infant feeding patterns and milk consumption with cow's milk protein antibody titres were studied in 697 newly-diagnosed diabetic children, 415 sibling-control children and 86 birth-dateand sex-matched population-based control children in the nationwide "Childhood Diabetes in Finland" study. IgA and IgG antibody titres to the proteins of cow's milk formula, BLG and BSA, and IgM antibody titres to cow's milk formula proteins were measured by ELISA. Several inverse correlations were observed between the duration of breast-feeding or age at introduction of dairy products and antibody titres, and positive correlations were observed between milk consumption and antibody titres in all three populations studied. Multivariate analyses which included the infant feeding variables, milk consumption and current age simultaneously showed that the earlier the introduction of dairy products and the greater the consumption of milk was, the higher several antibody titres were. High IgA antibody titres to cow's milk formula were associated with a greater risk of IDDM both among diabeticpopulation-control and diabetic-sibling-control pairs when adjusted for other cow's milk antibody titres, dietary variables and in diabetic-sibling-control pairs also for ICA. The results suggest that young age at introduction of dairy products and high milk consumption during childhood increase the levels of cow's milk antibodies and that high IgA antibodies to cow's milk formula are independently associated with increased risk of IDDM. [Diabetologia (1994) 37: 381-387]

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The Fourth International Serum Exchange Workshop to standardize cytoplasmic islet cell antibodies

Abstract: Report prepared by ~. Lernmark 1, J. L. Molenaar 2, W. A. M. van Beers 2' Y. Yamaguchi3; S. Nagataki 3' J. Ludvigsson 4 and N. K. Maclaren s on behalf of the Immunology and Diabetes Workshops and participating laboratories*

Cited by 71 publications

References 8 publications

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

Dietary manipulation of beta cell autoimmunity in infants at increased risk of type 1 diabetes: a pilot study

Diet, cow's milk protein antibodies and the risk of IDDM in Finnish children

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