Association between IA-2 autoantibody epitope specificities and age of onset in Japanese patients with autoimmune diabetes.

Abstract

The IA-2 is a major autoantigen of type 1 diabetes belonging to the protein tyrosine phosphatase family. We report on the humoral autoimmunity to an alternatively-spliced variant of IA-2 (IA-2 variant) and autoimmune-mediated diabetes age of onset association with IA-2 autoantibody epitope specificities, in 144 recent-onset patients with type 1 diabetes and 54 GAD autoantibody-positive patients with type 2 diabetes. The cytoplasmic domain of IA-2 (IA-2ic) detected a somewhat greater proportion of patients expressing autoantibodies than IA-2 variant (56%vs. 52% of patients with type 1 diabetes and 17%vs. 9% of GAD autoantibody-positive patients with type 2 diabetes). Conversely, only 1% of IA-2 variant autoantibody-positive patients failed to react to IA-2ic construct. Among 80 patients with type 1 diabetes who were positive for autoantibodies to IA-2ic, 8% recognized the juxtamembrane region (JM, representing amino acids 601-629) only, 64% bound the protein tyrosine phosphatase (PTP)-like domain of IA-2 only, and 29% bound both JM and PTP epitopes. Autoantibodies to the PTP-like domain were prevalent in children and adolescents with type 1 diabetes. The age of disease onset in patients with IA-2JM autoantibodies only, was significantly higher than those in patients reacted with the PTP-like domain of IA-2 (P< 0.02). Among GAD autoantibody-positive patients with type 2 diabetes reacted with IA-2ic, 44% bound the JM region only, and 33% bound epitopes in the PTP-like domain only; 22% had autoantibodies to both regions. The frequency of GAD autoantibody-positive patients with type 2 diabetes positive for autoantibodies to the JM region only, was significantly higher than that in patients with type 1 diabetes (P< 0.01). IA-2PTP autoantibodies were significantly associated with HLA-DR4, while the additional reactivity to IA-2JM was associated with HLA-DR9 allele. These results suggest that autoantibody recognition of IA-2 epitopes in autoimmune diabetes is associated with age of disease onset, which may reflect the intensity of the beta-cell destruction process.

• Authors: E Kawasaki, Y Sera, N Fujita, M Yamauchi, M Ozaki, T Abe, K Yamakawa, S Uotani, H Takino, H Yamasaki, Y Yamaguchi, Y Uchigata, N Matsuura, K Eguchi
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 17 Issue 4 Pg. 323-31 (Dec 2001) ISSN: 0896-8411 [Print] England
• PMID: 11771957 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Autoantibodies
• Epitopes
• ICA512 autoantibody

Topics

• Adolescent
• Adult
• Age of Onset
• Aged
• Antibody Specificity (immunology)
• Autoantibodies (immunology)
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (epidemiology, immunology, physiopathology)
• Epitopes (immunology)
• Female
• Humans
• Japan (epidemiology)
• Male
• Middle Aged