Anti-P110 autoantibodies identify a subtype of "seronegative" myasthenia gravis with prominent oculobulbar involvement

Mariapaola Marino, Amelia Evoli, Carlo Provenzano, Flavia Scuderi, Emanuela Bartoccioni

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and pathogenetic autoantibodies directed against the nicotinic acetylcholine receptor (seropositive myasthenia gravis; SPMG). Nearly 15% to 20% of MG patients do not have these antibodies (seronegative myasthenia gravis; SNMG), but several evidence indicate that these patients have circulating pathogenic autoantibodies directed against other muscle antigens. Using the TE671 rhabdomyosarcoma cell line as an antigen source, we analyzed sera from 63 SNMG and 26 SPMG patients and 26 healthy blood donors by FACS analysis. We found that 40 of 63 SNMG patients and only 1 of 26 SPMG patients had IgG binding to the TE671 cell line. None of the sera bound to the unrelated MRC5 cell line. To identify the antigen, we analyzed sera immunoreactivity in more detail by immunoprecipitation of biotinylated membrane proteins from TE671 cells. When the immunoprecipitated proteins were separated by SDS-PAGE electrophoresis and then transferred to nitrocellulose membranes, we found that SNMG IgG identify a band corresponding to a protein with a molecular weight of 110 kDa (P110), which is not recognized by seropositive MG sera. This anti-P110 immunoreactivity is significantly associated with a distinct clinical picture characterized by a prominent involvement of ocular and bulbar muscles, with frequent respiratory problems (p < 0.005), and is recognized by a specific antimuscle specific kinase (MUSK) antiserum. In a recent article, the presence of anti-MuSK antibodies was described in SNMG. Our results confirm the presence of these antibodies in SNMG and suggest that anti-Pl10/MuSK autoantibodies identify a subtype of SNMG in which the different pathogenesis induces the distinct clinical picture.
Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalLaboratory Investigation
Volume82
DOIs
Publication statusPublished - 2002

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies
  • Child
  • Eye Diseases
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis
  • Oculomotor Muscles
  • Receptors, Cholinergic
  • Rhabdomyosarcoma
  • Tumor Cells, Cultured

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