title: Anti-titin antibodies in myasthenia gravis: tight association with thymoma and heterogeneity of nonthymoma patients.
abstract: 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.
authors.affiliation: INSERM U25, 161 rue de Sèvres, 75743 Paris CEDEX 15, France. yamamoto@necker.fr
authors.forename: A M
authors.initials: AM
authors.lastname: Yamamoto
authors.forename: P
authors.initials: P
authors.lastname: Gajdos
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.forename: C
authors.initials: C
authors.lastname: Tranchant
authors.forename: J M
authors.initials: JM
authors.lastname: Warter
authors.forename: L
authors.initials: L
authors.lastname: Gomez
authors.forename: C
authors.initials: C
authors.lastname: Bourquin
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000912:Antibodies, Neoplasm / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D064211:Connectin; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000097:blood* / Q000276:immunology; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology; D011494:Protein Kinases / Q000097:blood* / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013934:Thymectomy; D013945:Thymoma / Q000097:blood* / Q000276:immunology; D013953:Thymus Neoplasms / Q000097:blood* / Q000276:immunology
chemical_list: D000912:Antibodies, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D064211:Connectin; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; C577285:TTN protein, human; D011494:Protein Kinases