Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice
| Autor: | Canan Ulusoy, Erdem Tüzün, Socrates J. Tzartos, Güher Saruhan-Direskeneli, Premkumar Christadoss, Fred D. Finkelman, Ruksana Huda, Konstantinos Poulas, Selin Turan, Eunmi Kim, Vuslat Yilmaz, Richard T. Strait, Nikos Trakas, Athanasios Niarchos, Lamprini Skriapa, Paraskevi Zisimopoulou |
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| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Immunology Enzyme-Linked Immunosorbent Assay Mice Immunity Antibody Specificity Internal medicine Myasthenia Gravis medicine Immunology and Allergy Animals Interleukin 4 Cells Cultured Autoimmune disease Mice Knockout biology Receptor Protein-Tyrosine Kinases medicine.disease Isotype Myasthenia gravis Interleukin-10 Interleukin 10 Cytokine Endocrinology Gene Expression Regulation Immunoglobulin G biology.protein Immunization Interleukin-4 Lymph Nodes Antibody |
| Zdroj: | Clinical immunology (Orlando, Fla.). 151(2) |
| ISSN: | 1521-7035 |
| Popis: | Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness associated with acetylcholine receptor (AChR), muscle-specific receptor kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4)-antibodies. MuSK-antibodies are predominantly of the non-complement fixing IgG4 isotype. The MuSK associated experimental autoimmune myasthenia gravis (EAMG) model was established in mice to investigate immunoglobulin (Ig) and cytokine responses related with MuSK immunity. C57BL/6 (B6) mice immunized with 30 μg of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (> 80% incidence). Although mice immunized with 10 μg of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 μg MuSK. While MuSK immunization stimulated production of all antibody isotypes, non-complement fixing IgG1 was the dominant anti-MuSK Ig isotype in both sera and neuromuscular junctions. Moreover, MuSK immunized IgG1 knockout mice showed very low serum MuSK-antibody levels. Sera and MuSK-stimulated lymph node cell supernatants of MuSK immunized mice showed significantly higher levels of IL-4 and IL-10 (but not IFN-γ and IL-12), than those of CFA immunized mice. Our results suggest that through activation of Th2-type cells, anti-MuSK immunity promotes production of IL-4, which in turn activates anti-MuSK IgG1, the mouse analog of human IgG4. These findings might provide clues for the pathogenesis of other IgG4-related diseases as well as development of disease specific treatment methods (e.g. specific IgG4 inhibitors) for MuSK-related MG. |
| Databáze: | OpenAIRE |
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