Titin antibodies in “seronegative” myasthenia gravis: a new role for an old antigen
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 compli...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 March 2016
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| In: |
Journal of neuroimmunology
Year: 2016, Volume: 292, Pages: 108-115 |
| ISSN: | 1872-8421 |
| DOI: | 10.1016/j.jneuroim.2016.01.018 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.jneuroim.2016.01.018 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0165572816300182 
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| Author Notes: | 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, 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 27.03.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1872-8421 |
| DOI: | 10.1016/j.jneuroim.2016.01.018 |