A syngeneic rat recombinant fragment of the extracellular domain of the acetylcholine receptor (AChR) α-subunit (Rα1-205), administered orally, suppresses ongoing experimental autoimmune myasthenia gravis (EAMG) in rats. The underlying mechanism is a shift from Th1 to Th2 regulation as evidenced by downregulated mRNA expression levels of IFN-γ and TNF-α, upregulated IL-10, changes in anti-AChR IgG isotypes and diminished Th1 signaling via CD28/CTLA-4:B7. Unlike the xenogeneic fragment, the syngeneic Rα1-205 does not induce elevation in TGF-β and elicitation of autoregulatory cells. The ability to suppress EAMG by a non-immunogenic syngeneic fragment of AChR is encouraging and may in the future be applied for the treatment of myasthenia gravis in humans.
|Number of pages||9|
|Journal||Journal of Neuroimmunology|
|State||Published - Jul 2004|
Bibliographical noteFunding Information:
This work was supported by grants from The Muscular Dystrophy Association of America (MDA), The Association Francaise Contre les Myopathies (AFM), The European Commission (EC, No QLG1-CT-2001-10918 and QLRT-2001-00225), The Abramson Family Foundation and The Wood-Byer Foundation.
- Mucosal tolerance
- Myasthenia gravis
- Th1/Th2 cells