T-CELL RECOGNITION OF MUSCLE ACETYLCHOLINE-RECEPTOR SUBUNITS IN GENERALIZED AND OCULAR MYASTHENIA-GRAVIS

Objectives: Our purpose was to identify the muscle acetylcholine recep tor (AChR) subunits recognized by autoimmune CD4(+) T cells in myasthe nia gravis (MG) and determine whether they differ in generalized (gMG) and ocular MG (oMG), and as gMG progresses. Methods: We tested the pr oliferative response of blood CD4(+) cells from 25 patients with gMG a nd four patients with oMG; to synthetic peptides spanning the sequence of each subunit of human muscle AChR. We also investigated the antisu bunit response of Th1 cells (a CD4(+) subset frequently involved in au toimmune phenomena) using an enzyme-linked immunospot (ELISPOT) assay of antigen-induced secretion of interferon-gamma by individual CD4(+) cells. Results: In gMG patients both the total CD4(+) population and t he Th1 subset recognized all AChR subunits to comparable extents. oMG patients recognized the AChR epsilon subunit minimally, and other subu nits consistently and more strongly. gMG patients whose disease had la sted less than 5 years had lower antisubunit responses, and several of them did not recognize some AChR subunits; patients whose disease had lasted for 5 or more years had higher antisubunit responses and alway s responded to all AChR subunits. Conclusions: CD4(+) and Th1 response s in MG involve the entire AChR molecule. This likely results from spr eading of the CD4(+) sensitization to increasingly larger parts of the AChR as the disease progresses. The differential recognition of AChR subunits in oMG might be related to the preferential involvement of ex trinsic ocular muscles, which express AChR containing the gamma subuni t.