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Selective silencing of auto-aggressive B cells in animal models of autoimmune diseases

English title Selective silencing of auto-aggressive B cells in animal models of autoimmune diseases
Applicant Izui Shozo
Number 110719
Funding scheme SCOPES
Research institution Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.10.2005 - 31.12.2007
Approved amount 54'000.00
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Keywords (5)

Autoimmunity; Systemic lupus erythematosus; Inhibitory receptors; Chimeric antibodies; Immunotherapy

Lay Summary (English)

Lay summary
The therapeutic approaches used at present to treat autoimmune diseases are not satisfactory as they are not targeted and induce either 1) general immunosuppression; 2) general suppression of inflammation or 3) a long-lasting elimination of all B cells regardless of their antigen specificity. We propose a novel strategy for the selective silencing of disease-associated autoreactive B cells.
The disease-associated DNA-specific B lymphocytes in SLE are logical targets for a selective therapeutic intervention. Our preliminary studies show that it is possible to inhibit selectively the production of IgG anti-DNA antibodies and to suppress disease activity in mice with spontaneous lupus by administering to them chimeric antibodies that cross-link their DNA-binding immunoglobulin receptors with inhibitory B cell receptors.
We shall produce a series of hybrid molecules by coupling monoclonal anti-mouse FcRIIB and anti-CD22 antibodies to DNA-mimotope peptides. Their immunomodulatory activity will be tested in young disease-free (6-7 weeks old) and sick (4-5 months old) lupus-prone MRL/lpr mice. Such chimeric antibodies may provide a platform for the development of highly selective therapeutic approaches in autoimmune diseases.
Direct link to Lay Summary Last update: 21.02.2013

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