3 Screen ELISA for High-Throughput Detection of Beta Cell Autoantibodies in Capillary Blood

Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decar...

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Veröffentlicht in:Diabetes technology & therapeutics Jg. 18; H. 11; S. 687
Hauptverfasser: Ziegler, Anette-G, Haupt, Florian, Scholz, Marlon, Weininger, Katharina, Wittich, Susanne, Löbner, Stephanie, Matzke, Claudia, Gezginci, Cigdem, Riethausen, Stephanie, Beyerlein, Andreas, Zillmer, Stephanie, Amoroso, Marie, Coles, Rebecca, Powell, Michael, Furmaniak, Jadwiga, Smith, Bernard Rees, Winkler, Christiane, Bonifacio, Ezio, Achenbach, Peter
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Sprache:Englisch
Veröffentlicht: United States 01.11.2016
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ISSN:1557-8593, 1557-8593
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Abstract Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies. An ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8 W/R-dimer molecules. The performance was determined in venous blood from 686 first-degree relatives of patients with type 1 diabetes, and 200 patients at onset of type 1 diabetes, and applied as a screening assay in capillary blood from 33,639 general population children. The 3 Screen assay sensitivity for detecting autoantibody-positive patients at onset of type 1 diabetes was similar to that achieved by separate radiobinding assays (RBAs) for antibodies to GAD, IA-2, and ZnT8. Results in venous and capillary serum were correlated (R = 0.987). At a threshold corresponding to the 98th centile (29.1 U/mL) of all 33,639 capillary samples, the 3 Screen was positive in 123 samples with two or more RBA-positive antibodies to insulin, GAD, IA-2, or ZnT8, 146 with one antibody, and 479 that were RBA negative for beta cell autoantibodies. A 3 Screen ELISA was developed that was suitable for first step screening of multiple beta cell autoantibodies in capillary blood.
AbstractList Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies. An ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8 W/R-dimer molecules. The performance was determined in venous blood from 686 first-degree relatives of patients with type 1 diabetes, and 200 patients at onset of type 1 diabetes, and applied as a screening assay in capillary blood from 33,639 general population children. The 3 Screen assay sensitivity for detecting autoantibody-positive patients at onset of type 1 diabetes was similar to that achieved by separate radiobinding assays (RBAs) for antibodies to GAD, IA-2, and ZnT8. Results in venous and capillary serum were correlated (R = 0.987). At a threshold corresponding to the 98th centile (29.1 U/mL) of all 33,639 capillary samples, the 3 Screen was positive in 123 samples with two or more RBA-positive antibodies to insulin, GAD, IA-2, or ZnT8, 146 with one antibody, and 479 that were RBA negative for beta cell autoantibodies. A 3 Screen ELISA was developed that was suitable for first step screening of multiple beta cell autoantibodies in capillary blood.
Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies.BACKGROUNDTesting for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We aimed to establish screening that utilized a first step assay (3 Screen) able to detect autoantibodies to the target antigens glutamic acid decarboxylase-65 (GAD), insulinoma-associated antigen 2 (IA-2), and zinc transporter 8 (ZnT8) to identify children positive for multiple beta cell autoantibodies.An ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8325W/R-dimer molecules. The performance was determined in venous blood from 686 first-degree relatives of patients with type 1 diabetes, and 200 patients at onset of type 1 diabetes, and applied as a screening assay in capillary blood from 33,639 general population children.METHODSAn ELISA format was used where plates were coated with a mixture of recombinant GAD, IA-2, and ZnT8325W/R-dimer molecules. The performance was determined in venous blood from 686 first-degree relatives of patients with type 1 diabetes, and 200 patients at onset of type 1 diabetes, and applied as a screening assay in capillary blood from 33,639 general population children.The 3 Screen assay sensitivity for detecting autoantibody-positive patients at onset of type 1 diabetes was similar to that achieved by separate radiobinding assays (RBAs) for antibodies to GAD, IA-2, and ZnT8. Results in venous and capillary serum were correlated (R = 0.987). At a threshold corresponding to the 98th centile (29.1 U/mL) of all 33,639 capillary samples, the 3 Screen was positive in 123 samples with two or more RBA-positive antibodies to insulin, GAD, IA-2, or ZnT8, 146 with one antibody, and 479 that were RBA negative for beta cell autoantibodies.RESULTSThe 3 Screen assay sensitivity for detecting autoantibody-positive patients at onset of type 1 diabetes was similar to that achieved by separate radiobinding assays (RBAs) for antibodies to GAD, IA-2, and ZnT8. Results in venous and capillary serum were correlated (R = 0.987). At a threshold corresponding to the 98th centile (29.1 U/mL) of all 33,639 capillary samples, the 3 Screen was positive in 123 samples with two or more RBA-positive antibodies to insulin, GAD, IA-2, or ZnT8, 146 with one antibody, and 479 that were RBA negative for beta cell autoantibodies.A 3 Screen ELISA was developed that was suitable for first step screening of multiple beta cell autoantibodies in capillary blood.CONCLUSIONA 3 Screen ELISA was developed that was suitable for first step screening of multiple beta cell autoantibodies in capillary blood.
Author Furmaniak, Jadwiga
Amoroso, Marie
Bonifacio, Ezio
Ziegler, Anette-G
Gezginci, Cigdem
Smith, Bernard Rees
Scholz, Marlon
Löbner, Stephanie
Powell, Michael
Winkler, Christiane
Beyerlein, Andreas
Wittich, Susanne
Riethausen, Stephanie
Weininger, Katharina
Coles, Rebecca
Matzke, Claudia
Zillmer, Stephanie
Achenbach, Peter
Haupt, Florian
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  givenname: Florian
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  surname: Matzke
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  givenname: Stephanie
  surname: Riethausen
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  organization: 1 Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München , Neuherberg, Germany
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  givenname: Andreas
  surname: Beyerlein
  fullname: Beyerlein, Andreas
  organization: 1 Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München , Neuherberg, Germany
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  surname: Zillmer
  fullname: Zillmer, Stephanie
  organization: 1 Institute of Diabetes Research, Helmholtz Zentrum München, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München , Neuherberg, Germany
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  surname: Amoroso
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  organization: 3 FIRS Laboratories , RSR Ltd., Parc Ty Glas, Llanishen, Cardiff, United Kingdom
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  surname: Powell
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  givenname: Bernard Rees
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  surname: Winkler
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  organization: 2 Forschergruppe Diabetes e.V. , Neuherberg, Germany
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  givenname: Ezio
  surname: Bonifacio
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  organization: 5 Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of Technische Universität , Dresden, Germany
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  surname: Achenbach
  fullname: Achenbach, Peter
  organization: 2 Forschergruppe Diabetes e.V. , Neuherberg, Germany
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Snippet Testing for beta cell autoantibodies is used for wide-scale identification of early stages of type 1 diabetes. This requires suitable screening assays. We...
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StartPage 687
SubjectTerms Adolescent
Autoantibodies - blood
Capillaries
Cation Transport Proteins - immunology
Child
Diabetes Mellitus, Type 1 - immunology
Enzyme-Linked Immunosorbent Assay - methods
Female
Glutamate Decarboxylase - immunology
Humans
Insulin-Secreting Cells - immunology
Male
Receptor-Like Protein Tyrosine Phosphatases, Class 8 - immunology
Sensitivity and Specificity
Zinc Transporter 8
Title 3 Screen ELISA for High-Throughput Detection of Beta Cell Autoantibodies in Capillary Blood
URI https://www.ncbi.nlm.nih.gov/pubmed/27552135
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