Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus

Diversification of autoimmunity to islet autoantigens is critical for progression to Type 1 diabetes. B-cells participate in diversification by modifying antigen processing, thereby influencing which peptides are presented to T-cells. In Type 1 diabetes, JM antibodies are associated with T-cell responses to PTP domain peptides. We investigated whether this is the consequence of close structural alignment of JM and PTP domain determinants on IA-2. Fab fragments of IA-2 antibodies with epitopes mapped to the JM domain blocked IA-2 binding of antibodies that recognise epitopes in the IA-2 PTP domain. Peptides from both the JM and PTP domains were protected from degradation during proteolysis of JM antibody:IA-2 complexes and included those representing major T-cell determinants in Type 1 diabetes. The results demonstrate close structural relationships between JM and PTP domain epitopes on IA-2. Stabilisation of PTP domain peptides during proteolysis in JM-specific B-cells may explain determinant spreading in IA-2 autoimmunity.

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Islet immunoisolation: experience with biopolymers

Risbud¹,

Bhonde²

2001

Journal of Biomaterials Science, Polymer Edition

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Incidence of Type I diabetes is increasing globally and has become a major health concern. There is enough evidence suggesting involvement of autoimmunity in destruction of insulin-producing islets of langerhans which leads to impaired glucose homeostasis. Islet transplantation is one of the approaches that received wide attention. Due to the autoimmune nature of the disease. strategies to protect transplanted islet graft from rejection are sought. Immunoisolation of islets inside semipermeable biocompatible materials is amongst them. Natural biopolymers have been used extensively as immunoisolation materials due to their satisfactory biocompatiblity and tissue tolerance. Here we attempt to address the need for islet immunoisolation and our experience in using natural biopolymers such as chitosan, cellulose and alginate for this application.

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Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus

Cited by 5 publications

References 13 publications

Autoimmunity in Insulin-Dependent Diabetes Mellitus

Autoimmunity in Insulin-Dependent Diabetes Mellitus

Relationships between major epitopes of the IA-2 autoantigen in Type 1 diabetes: Implications for determinant spreading

Islet immunoisolation: experience with biopolymers

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