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Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice

Ulusoy, Canan; Kim, Eunmi; Tuzun, Erdem; Huda, Ruksana; Yilmaz, Vuslat; Poulas, Konstantinos; Trakas, Nikos; Skriapa, Lamprini; Niarchos, Athanasios; Strait, Richard T.; Finkelman, Fred D.; Turan, Selin; Zisimopoulou, Paraskevi; Tzartos, Socrates; Saruhan-Direskeneli, Guher; Christadoss, Premkumar


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{
  "DOI": "10.1016/j.clim.2014.02.012", 
  "abstract": "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 mu g of recombinant human MuSK in incomplete or complete Freund's adjuvant (CFA) showed significant EAMG susceptibility (>80% incidence). Although mice immunized with 10 mu g of MuSK had lower EAMG incidence (14.3%), serum MuSK-antibody levels were comparable to mice immunized with 30 mu g 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-gamma 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. (c) 2014 Elsevier Inc. All rights reserved.", 
  "author": [
    {
      "family": "Ulusoy", 
      "given": " Canan"
    }, 
    {
      "family": "Kim", 
      "given": " Eunmi"
    }, 
    {
      "family": "Tuzun", 
      "given": " Erdem"
    }, 
    {
      "family": "Huda", 
      "given": " Ruksana"
    }, 
    {
      "family": "Yilmaz", 
      "given": " Vuslat"
    }, 
    {
      "family": "Poulas", 
      "given": " Konstantinos"
    }, 
    {
      "family": "Trakas", 
      "given": " Nikos"
    }, 
    {
      "family": "Skriapa", 
      "given": " Lamprini"
    }, 
    {
      "family": "Niarchos", 
      "given": " Athanasios"
    }, 
    {
      "family": "Strait", 
      "given": " Richard T."
    }, 
    {
      "family": "Finkelman", 
      "given": " Fred D."
    }, 
    {
      "family": "Turan", 
      "given": " Selin"
    }, 
    {
      "family": "Zisimopoulou", 
      "given": " Paraskevi"
    }, 
    {
      "family": "Tzartos", 
      "given": " Socrates"
    }, 
    {
      "family": "Saruhan-Direskeneli", 
      "given": " Guher"
    }, 
    {
      "family": "Christadoss", 
      "given": " Premkumar"
    }
  ], 
  "container_title": "CLINICAL IMMUNOLOGY", 
  "id": "63409", 
  "issue": "2", 
  "issued": {
    "date-parts": [
      [
        2014, 
        1, 
        1
      ]
    ]
  }, 
  "page": "155-163", 
  "title": "Preferential production of IgG1, IL-4 and IL-10 in MuSK-immunized mice", 
  "type": "article-journal", 
  "volume": "151"
}
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