The detection of low density lipoprotein-4 (LRP4) antibodies in double seronegative (dSN) myasthenia gravis (MG) patients has provided new insights in the diagnosis and treatment of MG. However, there are limited data regarding the clinical presentation and treatment response in dSN MG patients with LRP4-antibodies. We present a case series of three Caucasian dSN MG patients with positive LRP4-antibodies sharing a common ethnic background that presented with isolated ocular symptoms (MGFA I). The demographic and clinical characteristics, the diagnostic work-up as well as the treatment response during a follow-up period of 12-24 months are described in detail. All patients were treated successfully with acetylcholinesterase inhibitors (AcheI) and prednisone with two exhibiting full remission of their symptoms, while the remaining exhibited mild residual diplopia. Notably, we documented no signs of generalized disease progression, while no patient required immunosuppressive treatment. In conclusion, the distinct clinical phenotype of our patients highlights the clinical relevance of screening for LRP4-antibodies in patients presenting with isolated ocular MG independent of age and gender, since it may lead to the timely diagnosis of MG and prompt initiation of effective therapy with ACheI and corticosteroids.

• Klíčová slova
• Antibodies, Diagnosis, LRP4, Myasthenia, Ocular, Treatment,
• MeSH
• blefaroptóza farmakoterapie   imunologie   MeSH
• cholinesterasové inhibitory terapeutické užití   MeSH
• diplopie farmakoterapie   imunologie   MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis farmakoterapie   imunologie   MeSH
• prednison terapeutické užití   MeSH
• proteiny související s LDL-receptory imunologie   MeSH
• pyridostigmin-bromid terapeutické užití   MeSH
• senioři nad 80 let MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cholinesterasové inhibitory MeSH
• glukokortikoidy MeSH
• LRP4 protein, human MeSH Prohlížeč
• prednison MeSH
• proteiny související s LDL-receptory MeSH
• pyridostigmin-bromid MeSH

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.

• Klíčová slova
• Autoantibodies, Diagnosis, Myasthenia gravis, Radioimmunoprecipitation assay, Seronegative, Titin,
• MeSH
• autoprotilátky krev   MeSH
• ELISA MeSH
• konektin imunologie   MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• myasthenia gravis krev   diagnóza   epidemiologie   MeSH
• proteiny související s LDL-receptory imunologie   MeSH
• radioimunoprecipitační analýza MeSH
• receptory cholinergní imunologie   MeSH
• tyrosinkinasové receptory imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• konektin MeSH
• LRP4 protein, human MeSH Prohlížeč
• MUSK protein, human MeSH Prohlížeč
• proteiny související s LDL-receptory MeSH
• receptory cholinergní MeSH
• tyrosinkinasové receptory MeSH

• MeSH
• lidé MeSH
• myasthenia gravis krev   farmakoterapie   imunologie   MeSH
• nervosvalové spojení imunologie   MeSH
• prednison terapeutické užití   MeSH
• proteiny související s LDL-receptory imunologie   MeSH
• protilátky krev   MeSH
• receptory cholinergní imunologie   MeSH
• senioři MeSH
• sérologické testy MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• LRP4 protein, human MeSH Prohlížeč
• prednison MeSH
• proteiny související s LDL-receptory MeSH
• protilátky MeSH
• receptory cholinergní MeSH

Seronegative myasthenia gravis (MG) presents a serious gap in MG diagnosis and understanding. We applied a cell based assay (CBA) for the detection of muscle specific kinase (MuSK) antibodies undetectable by radioimmunoassay. We tested 633 triple-seronegative MG patients' sera from 13 countries, detecting 13% as positive. MuSK antibodies were found, at significantly lower frequencies, in 1.9% of healthy controls and 5.1% of other neuroimmune disease patients, including multiple sclerosis and neuromyelitis optica. The clinical data of the newly diagnosed MuSK-MG patients are presented. 27% of ocular seronegative patients were MuSK antibody positive. Moreover, 23% had thymic hyperplasia suggesting that thymic abnormalities are more common than believed.

• Klíčová slova
• Autoantibodies, Cell based assay, Diagnosis, MuSK, Myasthenia gravis,
• MeSH
• autoprotilátky krev   MeSH
• dospělí MeSH
• hyperplazie thymu diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• myasthenia gravis krev   diagnóza   patologie   MeSH
• neuromyelitis optica diagnóza   MeSH
• proteiny související s LDL-receptory imunologie   MeSH
• průtoková cytometrie MeSH
• radioimunoanalýza MeSH
• receptory cholinergní imunologie   MeSH
• senioři MeSH
• thymus patologie   MeSH
• tyrosinkinasové receptory imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• LRP4 protein, human MeSH Prohlížeč
• proteiny související s LDL-receptory MeSH
• receptory cholinergní MeSH
• tyrosinkinasové receptory MeSH