Other Autoantigens in MG

Seronegative MG patients are those patients who have clinical MG but do not demonstrate anti-AChR antibodies in blood. Some of these patients have anti-MuSK antibodies (up to 40% of this subgroup). Other ethnic groups or locations (e.g., Chinese and Norwegians) have lower frequencies of anti-MuSK antibodies in seronegative MG patients. MG patients with anti-MuSK antibodies do not have anti- AChR Abs, except as reported in a group of Japanese patients [16].

Agrin/MuSK signaling pathway maintains the structural and functional integrity of the postsynaptic NMJ apparatus in the adult muscle cell. Anti-MuSK antibodies affect the agrin-dependent AChR cluster maintenance at the NMJ, leading to reduced AChR numbers. Complement-mediated damage may also be responsible for decreasing the AChR numbers at the NMJ when targeted by anti-MuSK Abs. Some human muscle cell culture studies have shown cell cycle arrest, downregula- tion of AChR subunit with rapsyn, and other muscle protein expression, on exposure to sera from anti-MuSK-positive MG patients [2]. Other antimuscle cell protein antibodies (e.g., antititin and antiryanodine receptor antibodies) are also postulated to have pathogenic roles in autoimmune MG.