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Content archived on 2024-04-30

Novel diagnostics and therapy in Addison's disease and related autoimmunities

Objective


Foreseen Results

Recently, our groups have shown that the target antigens in the adrenal cortex and the gonads are the members of the steroidogenic enzymes, notably 21-hydroxylase (P450c21), 17-hydroxylase (P450c17) and the side-chain cleavage enzyme (P450scc). These keys findings have opened up new insights into the understanding of Addison's disease and associated autoimmune disorders. We now plan to continue these studies with following specific objectives: 1) preparation of recombinant adrenal and related autoantigens, 2) identification of B cell epitopes in the steroidogenic enzyme autoantigens and subsequent development of diagnostic tests, 3)characterization of the helper T cell and cytotoxic T cells responses toward these antigens and identification of the corresponding T cell epitopes, 4)generation of animal models for Addison's disease in order to create B cell and T cell epitopes studies in relation with disease course and morphology; their usage for development of new immunodiagnostic tests and in immunotherapeutic studies, 5)immunotherapy with antagonistic T cell peptides, 6)to study the presence of antibodies to steroidogenic enzymes in related autoimmune diseases, 7) development of new immunodiagnostic test principles for industrial use, 8)use of new immunodiagnostic tests in autoimmunity reference laboratories. The joint Research Project belongs to the Fourth Framework Program Activity A2, RTD Targeted to Industry, subsector 9.3 (Application of biotechnologies in the development of vaccines, diagnostics and therapeutics). The priorities of the project are to provide new diagnostic and therapeutic tools based on studies on B cell and T cell autoepitopes, in natural (human) and experimental (animal) forms of disease using biotechnological methods, information exchange on basic and clinical level, and public awareness in participating countries. The project is also aimed at to stabilize RTD potential (scientific competence and facilities) in participating ECC laboratory.
The project has following specific objectives :

1. preparation of adrenal and related autoantigens by recombinant technologies;
2. identification of B cell epitopes in the steroidogenic enzyme autoantigens and the application of these findings in the development of diagnostic tests;
3. characterization of the helper T cell and cytotoxic T cells responses towards adrenal and gonadal autoantigens in the patient material and identification of the corresponding T cell epitopes. Application of these findings in the development of diagnostic tests and treatment regimes;
4. generation of animal models for autoimmune Addison's disease with the aim to follow disease course in association with intra- and intermolecular T- and B cell epitope spreading. Application of these findings in the development of diagnostic tests and treatment regimes;
5. immunotherapy of Addison's disease and related autoimmunities with antagonistic T cell peptides;
6. to study the presence of steroidogenic enzyme antibodies among patients with Addison's disease related autoimmune disorders (diabetes mellitus, etc.), characterization of reacting epitopes;
7. development of new immunodiagnostic test principles for industrial use;
8. use of new immunodiagnostic tests in autoimmunity reference laboratories.

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CSC - Cost-sharing contracts

Coordinator

University of Tampere
EU contribution
No data
Address

33101 Tampere
Finland

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Total cost

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Participants (3)

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