Researchers from Spain have identified an antibody that may aid in routine diagnosis of double-seronegative myasthenia gravis.
Double-seronegative myasthenia gravis (dSNMG) is a subgroup of patients with myasthenia gravis (MG) who do not have the two most common antibody markers: acetylcholine receptor (AchR) and muscle-specific tyrosine kinase (MuSK). The clinical symptoms are similar to generalized MG in terms of muscle weakness distribution, disease severity, and response to immunotherapy and plasma exchange.
However, the lack of a detectable pathogenic antibody or an autoimmune biomarker has hindered the diagnosis and clinical management of this subset of patients, especially in ocular forms of the disease. Often it is necessary to resort to electromyelography to establish the diagnosis. So, it is encouraging that there may be other antibodies that can serve as markers for myasthenia.
Previous reports show that cortactin, a protein that mediates acetylcholine receptor clustering at the neuromuscular junction, is a good candidate antigen in dSNMG. To learn more, investigators undertook a cross-sectional study of 250 patients with a definitive diagnosis of myasthenia to describe the frequency and clinical features of patients who have dSNMG with cortactin antibodies.
Cortactin antibodies were identified in 9 of 38 patients with dSNMG (23.7%), and zero of 29 controls. Three had MG, and 6 had ocular myasthenia, of which 2 eventually developed generalized MG.
The group with cortactin antibodies frequently had a mild form of myasthenia at onset (100.0% vs. 62.7%; P=0.03), showed fewer bulbar signs at maximal worsening (0% vs 41.3%; P=0.01) and were younger at disease onset (34.9 vs. 53.9 years; P=0.03).
Some patients with MG and AChR antibodies had cortactin antibodies, but at a significantly lower rate than those with dSNMG (P=0.02).
It is not clear from this article if cortactin antibody testing is commercially available or whether patients with this antibody responded preferentially to treatment with steroids or cholinesterase inhibitors. However, the authors conclude that detection of cortactin antibodies may be helpful in establishing a diagnosis of ocular myasthenia in patients who a double seronegative for AchR and MuSK antibodies.