Purchase this article with an account.
H.J. Kaminski, B. Hughes, J. Porter, A. Merriam, B. Gong, C. Richmonds; Gene Expression Profile of Experimental Autoimmune Myasthenia Gravis in Passive Induction Experimental Autoimmune Myasthenia Gravis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5729.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Myasthenia gravis (MG) is an autoimmune neuromuscular transmission disorder characterized by acetylcholine receptor (AChR) loss caused primarily by the action of anti–AChR antibodies that fix complement. Little information exists as to the mechanisms of complement induced neuromuscular junction injury. Further, the human disease has a predilection for extraocular muscle (EOM) involvement and therefore, we chose to evaluate EOM specifically utilizing the unbiased, broad manner utilizing DNA microarray. Methods: We induced EAMG in mice by injection of rat anti–AChR mAb and treated control mice with irrelevant antibody. EOM was harvested 48 hr later at the time of expected maximal disease for RNA isolation and probe preparation. The experiment was performed in triplicate. The difference in gene expression between EOM of control and EAMG mice was evaluated with Robust Multichip Average (RMA). Results: We observed a significant change in the expression of 204 genes in EAMG versus control mice (> 1.7 or <–1.7 fold change; P</= 0.05). Hierarchical clustering showed that EAMG samples were clearly separated from controls based on their gene expression profile. The majority of altered genes encode for immunoglobulin chains, chemokine ligands, cytokines, metabolic enzymes, cellular activation and transcription factors, and transport proteins. Genes encoding for transcription factors and immunoglobulin chains were down–regulated, whereas those encoding for transport proteins, metabolic enzymes, and the cytokine interleukin 20 were up–regulated. Conclusions: The identification of gene expression alterations after induction of neuromuscular junction injury with EAMG indicates that, downstream to the activation of complement, pathways exist that may be sites for therapeutic intervention.
This PDF is available to Subscribers Only