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


Ulusoy C. A. , KIM E., Tuzun E. , HUDA R., Yilmaz V. , Poulas K., ...Daha Fazla

CLINICAL IMMUNOLOGY, cilt.151, ss.155-163, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 151 Konu: 2
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.clim.2014.02.012
  • Dergi Adı: CLINICAL IMMUNOLOGY
  • Sayfa Sayıları: ss.155-163

Özet

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.