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Novel animal models of acetylcholine receptor antibody–related myasthenia gravis
Author(s) -
Tüzün Erdem,
Allman Windy,
Ulusoy Canan,
Yang Huan,
Christadoss Premkumar
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06773.x
Subject(s) - myasthenia gravis , acetylcholine receptor , immunology , isotype , antibody , autoimmunity , t cell , receptor , biology , medicine , immune system , monoclonal antibody
Experimental autoimmune myasthenia gravis (EAMG) in mice has been used to unravel the pathogenic mechanisms and to be used as a preclinical model of myasthenia gravis (MG). Induction of predominantly ocular EAMG in HLA‐DQ8 transgenic mice immunized with acetylcholine receptor (AChR) subunits demonstrated the importance of nonconformationally expressed AChR subunits in extraocular muscle involvement. Wild‐type (WT) and CD4 + T cell knockout (KO) C57BL/6 mice developed EAMG upon immunization with AChR in incomplete Freund's adjuvant plus lipopolysaccharide. AChR‐specific IgG2 + B cell frequencies, estimated by Alexa‐conjugated AChR, and AChR‐reactive IgG2b levels significantly correlated with the clinical grades of EAMG in WT mice. CD4 + T cell–deficient EAMG mice exhibited AChR antibodies mainly of the IgG2b isotype, emphasizing T helper–independent B cell activation pathways in EAMG induction. These novel EAMG models have suggested that diverse immunopathological mechanisms might contribute to EAMG or MG pathogenesis.