IA-2 autoantibody affinity in children at risk for type 1 diabetes

Stephanie Krause; Ruth Chmiel; Ezio Bonifacio; Marlon Scholz; Michael Powell; Jadwiga Furmaniak; Bernard Rees Smith; Anette G. Ziegler; Peter Achenbach

doi:10.1016/j.clim.2012.09.010

IA-2 autoantibody affinity in children at risk for type 1 diabetes

Stephanie Krause, Ruth Chmiel, Ezio Bonifacio, Marlon Scholz, Michael Powell, Jadwiga Furmaniak, Bernard Rees Smith, Anette G. Ziegler, Peter Achenbach

Department of Pediatric Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 10⁷ to 10¹¹L/mol and was high (>1.0×10⁹L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development.

Original language	English
Pages (from-to)	224-229
Number of pages	6
Journal	Clinical Immunology
Volume	145
Issue number	3
DOIs	https://doi.org/10.1016/j.clim.2012.09.010
State	Published - Dec 2012

Keywords

Affinity
Diabetes risk
Epitopes
IA-2 autoantibodies
Type 1 diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.clim.2012.09.010

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title = "IA-2 autoantibody affinity in children at risk for type 1 diabetes",

abstract = "Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 107 to 1011L/mol and was high (>1.0×109L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development.",

keywords = "Affinity, Diabetes risk, Epitopes, IA-2 autoantibodies, Type 1 diabetes",

author = "Stephanie Krause and Ruth Chmiel and Ezio Bonifacio and Marlon Scholz and Michael Powell and Jadwiga Furmaniak and {Rees Smith}, Bernard and Ziegler, {Anette G.} and Peter Achenbach",

note = "Funding Information: This study was supported in part by grants from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.) and to the Competence Network for Diabetes mellitus (FKZ 01GI0805), and from the European Union ( EP7-HEALTH-2007 , DIAPREPP N202013 ). Peter Achenbach received support from Juvenile Diabetes Research Foundation ( 11-2005-1117 ). The authors thank Claudia Matzke, Daniela H{\"o}felmann and Annette Knopff for technical support, and Christiane Winkler, Markus Walter and Michael Hummel for clinical assistance. None of the funding sources have been involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.",

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doi = "10.1016/j.clim.2012.09.010",

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T1 - IA-2 autoantibody affinity in children at risk for type 1 diabetes

AU - Krause, Stephanie

AU - Chmiel, Ruth

AU - Bonifacio, Ezio

AU - Scholz, Marlon

AU - Powell, Michael

AU - Furmaniak, Jadwiga

AU - Rees Smith, Bernard

AU - Ziegler, Anette G.

AU - Achenbach, Peter

N1 - Funding Information: This study was supported in part by grants from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.) and to the Competence Network for Diabetes mellitus (FKZ 01GI0805), and from the European Union ( EP7-HEALTH-2007 , DIAPREPP N202013 ). Peter Achenbach received support from Juvenile Diabetes Research Foundation ( 11-2005-1117 ). The authors thank Claudia Matzke, Daniela Höfelmann and Annette Knopff for technical support, and Christiane Winkler, Markus Walter and Michael Hummel for clinical assistance. None of the funding sources have been involved in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

PY - 2012/12

Y1 - 2012/12

N2 - Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 107 to 1011L/mol and was high (>1.0×109L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development.

AB - Autoantibodies to insulinoma-associated protein 2 (IA-2A) are associated with increased risk for type 1 diabetes. Here we examined IA-2A affinity and epitope specificity to assess heterogeneity in response intensity in relation to pathogenesis and diabetes risk in 50 children who were prospectively followed from birth. At first IA-2A appearance, affinity ranged from 107 to 1011L/mol and was high (>1.0×109L/mol) in 41 (82%) children. IA-2A affinity was not associated with epitope specificity or HLA class II haplotype. On follow-up, affinity increased or remained high, and IA-2A were commonly against epitopes within the protein tyrosine phosphatase-like IA-2 domain and the homologue protein IA-2β. IA-2A were preceded or accompanied by other islet autoantibodies in 49 (98%) children, of which 34 progressed to diabetes. IA-2A affinity did not stratify diabetes risk. In conclusion, the IA-2A response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development.

KW - Affinity

KW - Diabetes risk

KW - Epitopes

KW - IA-2 autoantibodies

KW - Type 1 diabetes

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SN - 1521-6616

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SP - 224

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JO - Clinical Immunology

JF - Clinical Immunology

IS - 3

ER -

IA-2 autoantibody affinity in children at risk for type 1 diabetes

Abstract

Keywords

UN SDGs

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