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. Kleopa & 19 others E. 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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 - Mar 15 2016

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Connectin
Myasthenia Gravis
Antigens
Antibodies
Radioimmunoprecipitation Assay
Neuromuscular Junction
Muscular Diseases
Autoimmune Diseases

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen. / 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.; Kleopa, K. A.; Zamba-Papanicolaou, E.; Kyriakides, T.; Kostera-Pruszczyk, A.; Szczudlik, P.; Szyluk, B.; Lavrnic, D.; Basta, I.; Peric, S.; Tallaksen, C.; Maniaol, A.; Gilhus, N. E.; Casasnovas Pons, C.; Pitha, J.; Jakubíkova, M.; Hanisch, F.; Bogomolovas, J.; Labeit, D.; Labeit, S.; Tzartos, S. J.

In: Journal of Neuroimmunology, Vol. 292, 15.03.2016, p. 108-115.

Research output: Contribution to journalArticle

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, Kleopa, KA, Zamba-Papanicolaou, E, Kyriakides, T, Kostera-Pruszczyk, A, Szczudlik, P, Szyluk, B, Lavrnic, D, Basta, I, Peric, S, Tallaksen, C, Maniaol, A, Gilhus, NE, Casasnovas Pons, C, Pitha, J, Jakubíkova, M, Hanisch, F, Bogomolovas, J, Labeit, D, Labeit, S & Tzartos, SJ 2016, 'Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen', Journal of Neuroimmunology, vol. 292, pp. 108-115. https://doi.org/10.1016/j.jneuroim.2016.01.018
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. ; Kleopa, K. A. ; Zamba-Papanicolaou, E. ; Kyriakides, T. ; Kostera-Pruszczyk, A. ; Szczudlik, P. ; Szyluk, B. ; Lavrnic, D. ; Basta, I. ; Peric, S. ; Tallaksen, C. ; Maniaol, A. ; Gilhus, N. E. ; Casasnovas Pons, C. ; Pitha, J. ; Jakubíkova, M. ; Hanisch, F. ; Bogomolovas, J. ; Labeit, D. ; Labeit, S. ; Tzartos, S. J. / Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen. In: Journal of Neuroimmunology. 2016 ; Vol. 292. pp. 108-115.
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AU - Stergiou, C.

AU - Lazaridis, K.

AU - Zouvelou, V.

AU - Tzartos, J.

AU - Mantegazza, R.

AU - Antozzi, C.

AU - Andreetta, F.

AU - Evoli, A.

AU - Deymeer, F.

AU - Saruhan-Direskeneli, G.

AU - Durmus, H.

AU - Brenner, T.

AU - Vaknin, A.

AU - Berrih-Aknin, S.

AU - Behin, A.

AU - Sharshar, T.

AU - De Baets, M.

AU - Losen, M.

AU - Martinez-Martinez, P.

AU - Kleopa, K. A.

AU - Zamba-Papanicolaou, E.

AU - Kyriakides, T.

AU - Kostera-Pruszczyk, A.

AU - Szczudlik, P.

AU - Szyluk, B.

AU - Lavrnic, D.

AU - Basta, I.

AU - Peric, S.

AU - Tallaksen, C.

AU - Maniaol, A.

AU - Gilhus, N. E.

AU - Casasnovas Pons, C.

AU - Pitha, J.

AU - Jakubíkova, M.

AU - Hanisch, F.

AU - Bogomolovas, J.

AU - Labeit, D.

AU - Labeit, S.

AU - Tzartos, S. J.

PY - 2016/3/15

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N2 - 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.

AB - 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.

KW - Autoantibodies

KW - Diagnosis

KW - Myasthenia gravis

KW - Radioimmunoprecipitation assay

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