TY - JOUR
T1 - Titin antibodies in "seronegative" myasthenia gravis - A new role for an old antigen
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 - Jakubikova, M.
AU - Hanisch, F.
AU - Bogomolovas, J.
AU - Labeit, D.
AU - Labeit, S.
AU - Tzartos, S. J.
PY - 2016/3/15
Y1 - 2016/3/15
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 similar to 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 similar to 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 - Myasthenia gravis
KW - Seronegative
KW - Titin
KW - Autoantibodies
KW - Diagnosis
KW - Radioimmunoprecipitation assay
U2 - 10.1016/j.jneuroim.2016.01.018
DO - 10.1016/j.jneuroim.2016.01.018
M3 - Article
C2 - 26943968
SN - 0165-5728
VL - 292
SP - 108
EP - 115
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
ER -