Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen

C. Stergiou, K. Lazaridis, V. Zouvelou, J. Tzartos, R. Mantegazza, C. Antozzi, F. Andreetta, A. Evoli, F. Deymeer, G. Saruhan-Direskeneli, H. Durmus, T. Brenner, A. Vaknin, S. Berrih-Aknin, A. Behin, T. Sharshar, M. De Baets, M. Losen, P. Martinez-Martinez, K. A. KleopaE. Zamba-Papanicolaou, T. Kyriakides, A. Kostera-Pruszczyk, P. Szczudlik, B. Szyluk, D. Lavrnic, I. Basta, S. Peric, C. Tallaksen, A. Maniaol, N. E. Gilhus, C. Casasnovas Pons, J. Pitha, M. Jakubíkova, F. Hanisch, J. Bogomolovas, D. Labeit, S. Labeit, S. J. Tzartos

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Abstract

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction of skeletal muscles. Triple-seronegative MG (tSN-MG, without detectable AChR, MuSK and LRP4 antibodies), which accounts for ~ 10% of MG patients, presents a serious gap in MG diagnosis and complicates differential diagnosis of similar disorders. Several AChR antibody positive patients (AChR-MG) also have antibodies against titin, usually detected by ELISA. We have developed a very sensitive radioimmunoprecipitation assay (RIPA) for titin antibodies, by which many previously negative samples were found positive, including several from tSN-MG patients. The validity of the RIPA results was confirmed by western blots. Using this RIPA we screened 667 MG sera from 13 countries; as expected, AChR-MG patients had the highest frequency of titin antibodies (40.9%), while MuSK-MG and LRP4-MG patients were positive in 14.6% and 16.4% respectively. Most importantly, 13.4% (50/372) of the tSN-MG patients were also titin antibody positive. None of the 121 healthy controls or the 90 myopathy patients, and only 3.6% (7/193) of other neurological disease patients were positive. We thus propose that the present titin antibody RIPA is a useful tool for serological MG diagnosis of tSN patients.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalJournal of Neuroimmunology
Volume292
DOIs
Publication statusPublished - 15 Mar 2016

Keywords

  • Autoantibodies
  • Diagnosis
  • Myasthenia gravis
  • Radioimmunoprecipitation assay
  • Seronegative
  • Titin

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    Stergiou, C., Lazaridis, K., Zouvelou, V., Tzartos, J., Mantegazza, R., Antozzi, C., Andreetta, F., Evoli, A., Deymeer, F., Saruhan-Direskeneli, G., Durmus, H., Brenner, T., Vaknin, A., Berrih-Aknin, S., Behin, A., Sharshar, T., De Baets, M., Losen, M., Martinez-Martinez, P., ... Tzartos, S. J. (2016). Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen. Journal of Neuroimmunology, 292, 108-115. https://doi.org/10.1016/j.jneuroim.2016.01.018