Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients

Arch Neurol. 2001 Jun;58(6):885-90. doi: 10.1001/archneur.58.6.885.


Background: Titin is the major autoantigen recognized by anti-striated muscle antibodies, which are characteristic of generalized myasthenia gravis (MG).

Objective: To seek a correlation between anti-titin antibodies and other features of MG patients, including histopathology, age at diagnosis, anti-acetylcholine receptor (anti-AChR), autoantibody titers, and clinical severity.

Methods: A novel, highly specific radioligand assay was performed on a large group of 398 patients with generalized MG.

Results: Among thymectomized patients, anti-titin antibodies were present in most patients with thymoma (56/70 [80%]), contrasting with only a minority of patients with thymus atrophy or hyperplasia (17/165 [10%]). They were also present in 64 (41%) of 155 nonthymectomized patients who had a radiologically normal thymus. In these patients and in those who had a histologically normal thymus, anti-titin antibodies were associated with a later age at onset of disease and with intermediate titers of anti-AChR antibodies. After controlling for these 2 variables, disease severity was not significantly influenced by anti-titin antibodies.

Conclusions: Anti-titin antibodies are a sensitive marker of thymoma associated with MG in patients 60 years and younger, justifying the insistent search for a thymoma in MG patients of this age group who have these antibodies. In nonthymoma patients, anti-titin antibodies represent an interesting marker complementary to the anti-AChR antibody titer, identifying a restricted subset of patients. These clinical correlations should prompt further studies to examine the mechanisms leading to the production of anti-titin antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antibodies, Neoplasm / blood*
  • Antibodies, Neoplasm / immunology
  • Biomarkers / blood
  • Biomarkers, Tumor / blood
  • Connectin
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / blood*
  • Muscle Proteins / immunology
  • Myasthenia Gravis / blood*
  • Myasthenia Gravis / immunology
  • Protein Kinases / blood*
  • Protein Kinases / immunology
  • Receptors, Cholinergic / immunology
  • Receptors, Cholinergic / metabolism*
  • Statistics, Nonparametric
  • Thymectomy
  • Thymoma / blood*
  • Thymoma / immunology
  • Thymus Neoplasms / blood*
  • Thymus Neoplasms / immunology


  • Antibodies, Neoplasm
  • Biomarkers
  • Biomarkers, Tumor
  • Connectin
  • Muscle Proteins
  • Receptors, Cholinergic
  • TTN protein, human
  • Protein Kinases