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J Neuroimmunol. 2016 Mar 15;292:108-15. doi: 10.1016/j.jneuroim.2016.01.018. Epub 2016 Jan 27.

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

Author information

1
Hellenic Pasteur Institute, Athens, Greece; Tzartos NeuroDiagnostics, Athens, Greece.
2
Hellenic Pasteur Institute, Athens, Greece.
3
Neurology Department, Aeginition Hospital, Athens, Greece.
4
Neurological Institute "C. Besta", Milano, Italy.
5
Institute of Neurology, Catholic University, Rome, Italy.
6
Istanbul University, Istanbul, Turkey.
7
Hadassah Hebrew University Medical Center, Jerusalem, Israel.
8
UPMC and INSERM, Paris, France.
9
Raymond Poincaré Hospital, Garches, France.
10
School for Mental Health and Neuroscience, Maastricht University, The Netherlands.
11
The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
12
Department of Neurology, Medical University of Warsaw, Poland.
13
Neurology Clinic, Clinical Center of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.
14
Norway Department of Neurology, Ullevaal University Hospital, Oslo, Norway; Faculty of Medicine, Olso University, Norway.
15
Norway Department of Neurology, Ullevaal University Hospital, Oslo, Norway.
16
Department of Clinical Medicine, University of Bergen, Norway.
17
Bellvitge University Hospital, Barcelona, Spain.
18
Department of Neurology and Clinical Neuroscience Center, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague, Czech Republic.
19
Universitätsklinikum Halle, Halle, Germany.
20
Faculty of Clinical Medicine Manheim, University of Heidelberg, Germany.
21
Faculty of Clinical Medicine Manheim, University of Heidelberg, Germany; Myomedix GmbH, 69151 Neckargemuend, Germany.
22
Hellenic Pasteur Institute, Athens, Greece; Tzartos NeuroDiagnostics, Athens, Greece. Electronic address: stzartos@gmail.com.

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.

KEYWORDS:

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

PMID:
26943968
DOI:
10.1016/j.jneuroim.2016.01.018
[Indexed for MEDLINE]

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