Novel autoimmune targets and crossreactivity in myasthenia gravis

Abstract

The identification of the AChR as the antigenic target in the autoimmune disease MG stemmed from advances in understanding of the structure of the neuromuscular junction. The improved understanding of the structure of the synapse is being associated, concomitantly, with improved understanding of the antigenic targets of autoimmune disease of the neuromuscular junction. Intramolecular and inter-molecular spreading of antigenic targets appears to occur at the synapse and may explain the development of antibodies against cytoskeletal proteins in patients whose initial immune attack is directed against the AChR. Immune responses directed exclusively against these cytoskeletal proteins however may explain the phenomenon of seronegative myasthenia gravis. Molecular mimickry with crossreactive immune responses may explain the development of anti-AChR, anti-titin and anti-ryanodine receptor antibodies in patients with thymoma and MG. The chemical reactivity of proteins at the synapse may also render them susceptible to immune attack as a consequence of altered structure.