Diagnostic utility of cortactin antibodies in myasthenia gravis

Isabel Illa, Elena Cortés-Vicente, María Ángeles Martínez, Eduard Gallardo

Research output: Contribution to journalReview articleResearchpeer-review

15 Citations (Scopus)

Abstract

© 2017 New York Academy of Sciences. 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 anticortactin antibodies. In contrast, patients with AChR+ MGor 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+ MGpatients (P=0.02). None of theMuSK+ MGpatients, 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 generalizedMGwithout bulbar symptoms. We conclude that cortactin autoantibodies are biomarkers of MG that, when present, suggest that the disease will be mild.
Original languageEnglish
Pages (from-to)90-94
JournalAnnals of the New York Academy of Sciences
Volume1412
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • Acetylcholine receptor
  • Cortactin antibodies
  • MuSK
  • Myasthenia gravis

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