Target silencing of disease-associated B-lymphocytes by chimeric molecules in SCID model of pristane-induced autoimmunity
| Autor: | Andrey Tchorbanov, Maria Nikolova, Kalina Nikolova, Iliyana Dimitrova, Nikolina Mihaylova, Vera Gesheva, Todor A. Todorov |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD32
Recombinant Fusion Proteins Receptors Antigen B-Cell Autoimmunity Mice SCID medicine.disease_cause Immunoglobulin G Cell Line Mice Rheumatology medicine Animals Humans Lupus Erythematosus Systemic Autoimmune disease B-Lymphocytes Mice Inbred BALB C Systemic lupus erythematosus biology Terpenes Receptors IgG Autoantibody DNA medicine.disease Molecular biology Fusion protein Rats Immunology biology.protein Cytokines Female Antibody Immunosuppressive Agents |
| Zdroj: | Lupus. 19(11) |
| ISSN: | 1477-0962 |
| Popis: | Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the generation of autoantibodies against a diverse array of self-antigens. The B cells producing immunoglobulin G (IgG) antibodies to double-stranded DNA appear to play a main role in the disease progression. Their specific elimination is a reasonable mechanism for effective therapy of SLE. The presently used approaches for silencing autoreactive disease-associated B cells are nonspecific and more precise therapies are needed. We have previously constructed a chimeric protein molecule consisting of several DNA-mimotope peptides coupled to a rat monoclonal anti-mouse CD32 (FcgRIIb) antibody. The mineral oil pristane induces a lupus-like syndrome in non-autoimmune mice leading to the development of glomerulonephritis and lupus-associated autoantibodies. In the present paper, using a pristane-induced autoimmune model in SCID mice, we analyzed the ability of the chimeric antibody to suppress selectively the autoreactive B lymphocytes by cross-linking B-cell surface immunoglobulin receptors with the inhibitory IgG FcgRIIb receptors. Treatment with DNA-like chimeric molecules inhibited B- and T-cell proliferation, restricted the number of anti-DNA antibody-producing cells and suppressed the generation of IgG anti-DNA antibodies. In contrast, phosphate buffered saline (PBS)-injected control mice experienced an increase of disease-associated antibody levels and developed glomerulonephritis similar to pristane-treated donor Balb/c mice. Lupus (2010) 0, 1–11. |
| Databáze: | OpenAIRE |
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