Stergiou, C. (6602298175)C. (6602298175)StergiouLazaridis, K. (56603256800)K. (56603256800)LazaridisZouvelou, V. (8535619100)V. (8535619100)ZouvelouTzartos, J. (23483327100)J. (23483327100)TzartosMantegazza, R. (7007022015)R. (7007022015)MantegazzaAntozzi, C. (7003634542)C. (7003634542)AntozziAndreetta, F. (6701660100)F. (6701660100)AndreettaEvoli, A. (7003290058)A. (7003290058)EvoliDeymeer, F. (6603952751)F. (6603952751)DeymeerSaruhan-Direskeneli, G. (55405118500)G. (55405118500)Saruhan-DireskeneliDurmus, H. (26767720100)H. (26767720100)DurmusBrenner, T. (7004884189)T. (7004884189)BrennerVaknin, A. (36572839600)A. (36572839600)VakninBerrih-Aknin, S. (7004839194)S. (7004839194)Berrih-AkninBehin, A. (24072944800)A. (24072944800)BehinSharshar, T. (7004157942)T. (7004157942)SharsharDe Baets, M. (14624885100)M. (14624885100)De BaetsLosen, M. (6507635956)M. (6507635956)LosenMartinez-Martinez, P. (8951108100)P. (8951108100)Martinez-MartinezKleopa, K.A. (6603667270)K.A. (6603667270)KleopaZamba-Papanicolaou, E. (6506279307)E. (6506279307)Zamba-PapanicolaouKyriakides, T. (7006056265)T. (7006056265)KyriakidesKostera-Pruszczyk, A. (20235055500)A. (20235055500)Kostera-PruszczykSzczudlik, P. (16308272100)P. (16308272100)SzczudlikSzyluk, B. (6505763786)B. (6505763786)SzylukLavrnic, D. (6602473221)D. (6602473221)LavrnicBasta, I. (8274374200)I. (8274374200)BastaPeric, S. (35750481700)S. (35750481700)PericTallaksen, C. (6701619496)C. (6701619496)TallaksenManiaol, A. (36053344700)A. (36053344700)ManiaolGilhus, N.E. (34770675300)N.E. (34770675300)GilhusCasasnovas Pons, C. (55995300800)C. (55995300800)Casasnovas PonsPitha, J. (23006350900)J. (23006350900)PithaJakubíkova, M. (48361571900)M. (48361571900)JakubíkovaHanisch, F. (7005111902)F. (7005111902)HanischBogomolovas, J. (25647616900)J. (25647616900)BogomolovasLabeit, D. (6603907948)D. (6603907948)LabeitLabeit, S. (7006443631)S. (7006443631)LabeitTzartos, S.J. (7007126407)S.J. (7007126407)Tzartos2025-07-022025-07-022016https://doi.org/10.1016/j.jneuroim.2016.01.018https://www.scopus.com/inward/record.uri?eid=2-s2.0-84960910874&doi=10.1016%2fj.jneuroim.2016.01.018&partnerID=40&md5=3658c258f5d3340258b79f9e264cbbadhttps://remedy.med.bg.ac.rs/handle/123456789/13431Myasthenia 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. © 2016 Elsevier B.V.AutoantibodiesDiagnosisMyasthenia gravisRadioimmunoprecipitation assaySeronegativeTitin