Diagnostic utility of cortactin antibodies in myasthenia gravis

Ann N Y Acad Sci. 2018 Jan;1412(1):90-94. doi: 10.1111/nyas.13502. Epub 2017 Oct 25.


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.

Keywords: MuSK; acetylcholine receptor; cortactin antibodies; myasthenia gravis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibody Specificity
  • Autoantibodies / blood*
  • Autoantigens / metabolism
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cortactin / immunology*
  • Humans
  • Models, Immunological
  • Myasthenia Gravis / diagnosis*
  • Myasthenia Gravis / immunology*
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptors, Cholinergic / immunology


  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • CTTN protein, human
  • Cortactin
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases