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Diagnostic utility of cortactin antibodies in myasthenia gravis.
Illa I1,2, Cortés-Vicente E1,2, Martínez MÁ3, Gallardo E1,2
Ann N Y Acad Sci. 2017 Oct 25. doi: 10.1111/nyas.13502.
Patients with myasthenia gravis (MG) without antibodies to the acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK) have been classified as having double-seronegative myasthenia gravis (dSNMG).
We used the sera from six dSNMG patients with positive immunohistochemistry assays in a protein array to screen reactivity with 9000 human proteins.
We identified cortactin, an intracellular protein that interacts with agrin/MuSK favoring AChR aggregation, as a new antigen in dSNMG.
We then designed an in-house enzyme-linked immunosorbent assay as a screening assay and confirmed these results by western blot. We found that 19.7% of dSNMG patients had anti-cortactin antibodies.
In contrast, patients with AChR+ MG or other autoimmune disorders and healthy controls were positive at significantly lower rates.
Five percent of healthy controls were positive.
In a recent study, we screened sera from 250 patients (AChR+ MG, MuSK+ MG, dSNMG) and 29 healthy controls.
Cortactin antibodies were identified in 23.7% of dSNMG and 9.5% AChR+ MG patients (P = 0.02). None of the MuSK+ MG patients, patients with other autoimmune disorders, or healthy controls had antibodies against cortactin.
Patients with dSNMG cortactin+ MG were negative for anti-striated muscle and anti-LRP4 antibodies. Patients with dSNMG cortactin+ MG presented ocular or mild generalized MG without bulbar symptoms.
We conclude that cortactin autoantibodies are biomarkers of MG that, when present, suggest that the disease will be mild.
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