IA-2 antibody isotypes and epitope specificity during the prediabetic process in children with HLA-conferred susceptibility to type I diabetes.

Abstract

The natural history of preclinical diabetes is partly characterized, but there is still limited information on the dynamics of the immune response to beta-cell autoantigens during the course of preclinical disease. The aim of this work was to assess the maturation of the humoral immune response to the protein tyrosine phosphatase(PTP)-related proteins (IA-2 and IA-2beta) in preclinical type I diabetes (TID). Forty-five children participating in the Finnish Type I Diabetes Prediction and Prevention (DIPP) Study who had seroconverted to IA-2 antibody positivity were analysed. Specific radiobinding assays were used to determine IA-2/IA-2beta epitope-specific antibodies (the juxtamembrane (JM) region of IA-2, PTP-like domain and betaPTP-like domain) and isotype-specific IA-2 antibodies. Individual areas under the curve (AUC) over the observation period were calculated for total IA-2 antibodies, each isotype and specific epitope responses. The children who progressed to TID tended to have an initial IA-2 JM epitope response more frequently (P = 0.06), and this response was more often dominant during the observation period (P < 0.05). The children who did not progress to TID had IgE-IA-2 more frequently (70%; versus progressors 27%; P < 0.05), and had higher integrated titres of IgE-IA-2 antibodies (P < 0.05). The occurrence of IgE-IA-2 antibodies was protective even when combined with positivity for IA-2 JM antibodies (P = 0.002). IgE-IA-2 antibody reactivity may be a marker of a regulatory immune response providing protection against or delaying progression to TID among IA-2 antibody-positive young children with HLA-conferred disease susceptibility.

• Authors: S Hoppu, T Härkönen, M S Ronkainen, S Simell, A Hekkala, A Toivonen, J Ilonen, O Simell, M Knip
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 144 Issue 1 Pg. 59-66 (Apr 2006) ISSN: 0009-9104 [Print] England
• PMID: 16542366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Epitopes
• HLA-DQ Antigens
• HLA-DQ beta-Chains
• HLA-DQB1 antigen
• ICA512 autoantibody
• Immunoglobulin A
• Immunoglobulin G
• Immunoglobulin Isotypes
• Immunoglobulin M
• Membrane Proteins
• PTPRN2 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases
• Receptor-Like Protein Tyrosine Phosphatases, Class 8

Topics

• Autoantibodies (immunology)
• Child, Preschool
• Cross Reactions (immunology)
• Diabetes Mellitus, Type 1 (immunology)
• Epitopes (immunology)
• Female
• Genotype
• HLA-DQ Antigens (genetics)
• HLA-DQ beta-Chains
• Humans
• Immunoglobulin A (immunology)
• Immunoglobulin G (immunology)
• Immunoglobulin Isotypes (immunology)
• Immunoglobulin M (immunology)
• Infant
• Male
• Membrane Proteins (immunology)
• Protein Tyrosine Phosphatase, Non-Receptor Type 1
• Protein Tyrosine Phosphatases (immunology)
• Receptor-Like Protein Tyrosine Phosphatases, Class 8
• Time Factors