TY - JOUR
T1 - MuSK induced experimental autoimmune myasthenia gravis does not require IgG1 antibody to MuSK
AU - Küçükerden, Melike
AU - Huda, Ruksana
AU - Tüzün, Erdem
AU - Yilmaz, Abdullah
AU - Skriapa, Lamprini
AU - Trakas, Nikos
AU - Strait, Richard T.
AU - Finkelman, Fred D.
AU - Kabadayi, Sevil
AU - Zisimopoulou, Paraskevi
AU - Tzartos, Socrates
AU - Christadoss, Premkumar
N1 - Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/6/15
Y1 - 2016/6/15
N2 - Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1 +, IgG2 + and IgG3 + peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis.
AB - Sera of myasthenia gravis (MG) patients with muscle-specific receptor kinase-antibody (MuSK-Ab) predominantly display the non-complement fixing IgG4 isotype. Similarly, mouse IgG1, which is the analog of human IgG4, is the predominant isotype in mice with experimental autoimmune myasthenia gravis (EAMG) induced by MuSK immunization. The present study was performed to determine whether IgG1 anti-MuSK antibody is required for immunized mice to develop EAMG. Results demonstrated a significant correlation between clinical severity of EAMG and levels of MuSK-binding IgG1 +, IgG2 + and IgG3 + peripheral blood B cells in MuSK-immunized wild-type (WT) mice. Moreover, MuSK-immunized IgG1 knockout (KO) and WT mice showed similar EAMG severity, serum MuSK-Ab levels, muscle acetylcholine receptor concentrations, neuromuscular junction immunoglobulin and complement deposit ratios. IgG1 and IgG3 were the predominant anti-MuSK isotypes in WT and IgG1 KO mice, respectively. These observations demonstrate that non-IgG1 isotypes can mediate MuSK-EAMG pathogenesis.
KW - Anti-MuSK IgG
KW - Experimental autoimmune myasthenia gravis
KW - MuSK-binding B cell
KW - Muscle specific kinase
KW - Myasthenia gravis
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U2 - 10.1016/j.jneuroim.2016.04.003
DO - 10.1016/j.jneuroim.2016.04.003
M3 - Article
C2 - 27235354
AN - SCOPUS:84966388989
SN - 0165-5728
VL - 295-296
SP - 84
EP - 92
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
ER -