title: Juvenile-onset myasthenia gravis: autoantibody status, clinical characteristics and genetic polymorphisms.
abstract: Myasthenia gravis (MG) is an autoimmune disorder mediated by antibodies against proteins at the neuromuscular junction. Juvenile-onset MG (JMG) has been reported to have special characteristics. It is still unclear whether there are any pathogenic and genetic differences between juvenile and adult MG. In this study, we evaluated the clinical characteristics, autoantibody status (antibodies against AChR, MuSK, LRP4, titin and RyR) and genetic susceptibility (CHRNA1, CTLA4 and AIRE) in 114 Chinese JMG patients, and compared with 207 young adult MG patients (onset age 18-40 years). JMG patients were classified into two subgroups: the very early onset group (<8 years) and puberty onset group (8-18 years). The very early onset MG patients had a higher proportion of ocular MG and thymus hyperplasia, compared with puberty onset MG and young adult MG (P < 0.05). AChR antibodies were found in majority of JMG patients and were associated with more severe disease (P < 0.05), while other antibodies were rare in JMG. Moreover, the very early onset MG had a more prominent genetic predisposition than puberty and adult MG, affecting the susceptible genes CHRNA1 and CTLA4. JMG has the same pathogenic background as adult MG, but has typical clinical features and a prominent genetic predisposition in very early onset patients (<8 years). Specific therapeutic considerations are needed.
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Yu
authors.identifier: http://orcid.org/0000-0002-3125-2855
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway.
authors.forename: Geir Olve
authors.initials: GO
authors.lastname: Skeie
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Zisimopoulou
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.|Tzartos NeuroDiagnostics, Athens, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Karagiorgou
authors.affiliation: Department of Neurobiology, Hellenic Pasteur Institute, Athens, Greece.|Tzartos NeuroDiagnostics, Athens, Greece.
authors.forename: Socrates J
authors.initials: SJ
authors.lastname: Tzartos
authors.affiliation: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China.
authors.forename: Yao-Xian
authors.initials: YX
authors.lastname: Yue
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Romi
authors.affiliation: Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Jinan, 250012, China. drlhf@163.com.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway. nils.gilhus@helse-bergen.no.|Department of Neurology, Haukeland University Hospital, 5021, Bergen, Norway. nils.gilhus@helse-bergen.no.
authors.forename: Nils Erik
authors.initials: NE
authors.lastname: Gilhus
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D044466:Asian People; D001323:Autoantibodies / Q000097:blood*; D060908:CTLA-4 Antigen / Q000235:genetics*; D004185:Disability Evaluation; D005260:Female; D005787:Gene Frequency; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000276:immunology; D008297:Male; D009157:Myasthenia Gravis / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D011110:Polymorphism, Genetic / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D060908:CTLA-4 Antigen; D026502:LDL-Receptor Related Proteins; D020794:Receptor Protein-Tyrosine Kinases; D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D014157:Transcription Factors; D000096927:AIRE Protein; C523021:CHRNA1 protein, human; C556706:CTLA4 protein, human; C551781:LRP4 protein, human; C095714:MUSK protein, human
keywords: Acetylcholine receptor; Cholinergic receptor nicotinic alpha 1 (CHRNA1); Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); Gene polymorphisms; Juvenile onset myasthenia gravis; Muscle specific kinase