Experimental myasthenia gravis. A murine system.

Abstract

Mice from eight inbred strains were immunized with acetylcholine receptor (AChR) purified from Torpedo californica. All mice developed high concentrations of serum antibodies (10(-6) M) against the immunogen and approximately 80% possessed antibodies reactive with mouse nicotinic AChR. 33% of the mice immunized (n = 236) developed muscular weakness and flaccid paralysis. Behavioral, electrophysiological, and pharmacological similarities were found between the experimentally induced muscular weakness and the disease myasthenia gravis. Susceptibility to experimental myasthenia was found to be strain dependent in that the frequency of paralysis was much greater in some strains than others. The occurrence of muscular weakness and flaccid paralysis did not correlate with the concentration of antibodies reactive with T. californica or mouse AChR. Anti-receptor antibodies which increased the rate of AChR degradation on the mouse muscle cell line, BC3H-1, were found in the serum of both myasthenic and nonmyasthenic mice. 40% of the mice tested possessed antibodies reactive with antigenic determinants present on mouse receptor but not T. californica receptor. The occurrence of antibodies unique to mouse receptor did not correlate with myasthenia. Thus, myasthenia in the mouse does not occur simply as a consequence of the presence of antibodies directed against cell surface antigenic determinants of AChR. If anti-AChR antibodies are both necessary and sufficient for the induction of myasthenia, then these studies suggest that populations of a particular structure and/or specificity are required. It is anticipated that the mouse model of myasthenia gravis will permit the regulation of the anti-receptor immune response to be studied in detail.

In vivo therapy with monoclonal anti-I-A antibody suppresses immune responses to acetylcholine receptor

“…2), antibody titers were 14.3 ± 4.9 X 10-1 1.l in the no-treatment group, 14.1 ± 4.7 X 10-l in the anti-I-Ab antibody group, and 9.0 ± 4.0 x 10-1 p1 in the anti-I-A' antibody group (P < 0.01 for anti-I-A' compared to no monoclonal or anti-I-Ab treatment). Similar results were obtained in a second experiment with 10 (10). Weakness was ameliorated (unless mice were moribund) within 5-10 min of administration of neostigmine bromide (0.0375 mg/kg) and atropine sulfate (0.015 mg/kg) intraperitoneally.…”

Transgenic Expression of IL-10 in T Cells Facilitates Development of Experimental Myasthenia Gravis

“…Thus, the absence or the presence of low amounts of anti-MAChR Ab in the serum may not correlate with absent or mild EMG symptoms. A lack of correlation between the concentration of anti-MAChR Ab and severity of EMG in mice has been described (33). Also in MG, there is poor or no correlation between the concentration of anti-AChR Ab in the serum and the symptom severity (4).…”

Split Tolerance in a Novel Transgenic Model of Autoimmune Myasthenia Gravis

“…In this model, mice are immunized with the AChR from Torpedo californica (T-AChR), resulting in the production of anti-T-AChR Abs, some of which cross-react with the mouse AChR causing the muscle weakness associated with disease (experimental autoimmune MG, EAMG) (19). It is clear that CD4…”