medwireNews: Patients who have myasthenia gravis (MG) are more likely to have a severe form of the disease and more difficulty achieving remission if they are seropositive for antibodies to muscle-specific kinase (MuSK), report researchers.
"These features should be considered by the clinician in the management of this particular form of MG," say Carlo Antozzi (Neurological Institute Foundation "Carlo Besta," Milan, Italy) and colleagues.
Anti-acetylcholine receptor (AChR) antibodies, the immunologic hallmark of MG, are detected in about 85% of MG patients (AChR-positive patients). The remaining AChR-negative patients may have antibodies to MuSK (MuSK-positive), while others do not and are therefore double negative (DN).
In a study of 677 patients followed up between January 1980 and December 2009, the clinical stage at onset and at maximal worsening was more severe in MuSK-positive patients (n=55) than in AChR-positive patients (n=517) and DN patients (n=105).
Clinical stages were graded using the following categories: ocular MG; generalized MG (involvement of limb and trunk muscles), bulbar MG (generalized MG with bulbar muscle involvement), respiratory MG (generalized or bulbar MG with respiratory compromise); pharmacologic remission, complete stable remission (CSR, no symptoms or signs of MG for at least 1 year without treatment); and death from MG.
As reported in Neurology, 60.1% of MuSK-positive patients had bulbar MG at onset, compared with 35.2% of AChR-positive individuals and 23.8% of DN individuals. And at maximal worsening, bulbar involvement was observed in 83.6% of MuSK-positive patients, compared with 58.6% of AChR-positive patients and 43.8% of DN patients.
Furthermore, CSR was achieved in only 3.6% of the MuSK-positive patients, compared with 22.2% of the AChR patients and 21.9% of the DN group.
Multivariate analysis revealed that across the entire cohort, disease onset before age 40 years and the presence of only ocular or generalized clinical stages at maximal worsening were significantly associated with the likelihood for reaching CSR, at hazard ratios of 1.96, 8.05, and 3.71, respectively.
"MuSK antibodies define a clinically different subgroup of patients with MG that, in our series, was associated with a lower occurrence of CSR," say Antozzi and colleagues.
"Indeed, MuSK antibodies belong to the immunoglobulin G4 subclass, do not bind complement, and cause disruption of the neuromuscular junction, and hence transmission, with a complex effect on several proteins involved in anchoring and stabilization of the AChR within the postsynaptic membrane," they explain.
The team says the low percentage of CSR achieved among the MuSK-positive patients suggests the need for more aggressive treatments from the onset, and that the use of corticosteroids and immunosuppressive drugs should probably be considered as early as possible.
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