Juvenile myasthenia gravis in Norway: Epidemiological, clinical, genetic and immunological studies
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AbstractJuvenile myasthenia gravis (JMG) is a rare autoimmune disease affecting the neuromuscular endplate, thus impairing the neuromuscular transmission giving fatigable muscle weakness. The disease is potentially lethal and correct diagnosis is essential since several treatment options including immunosuppressive medication and thymectomy, are available. The overall aim of this thesis was to characterize the clinical aspects of JMG in Norway, especially focusing on symptoms, comorbidity, treatment and long-term outcome, as well as genetic risk factors. JMG patients were identified through multiple strategies and 63 patients, classified as either prepubertal (<12 years) or postubertal (≤12 years) onset, were included in the clinical studies. A stable incidence rate of JMG of 1.6 per million over the last 25 years were found, higher among females and higher in the postpubertal age group. The clinical symptoms were most often generalized, and the generalization typically occurred within 2 years from onset. Outcome was overall good, and seemed especially favourable among the prepubertal cases. A second autoimmune disease occurred in 1/3 of the patients and was the most frequent comorbidity. The long-term effect of thymectomy on the immune system was also studied. We found indications of a premature immunosenescence in the T cell compartment in thymectomized juvenile MG patients; however, no increase in infection rate, autoimmune comorbidity or cancer was seen. Finally, concerning genetic risk factors, we identified a new risk allele, HLA-DRB1*04:04 in prepubertal onset JMG. HLA-B*08 known to be a major risk allele in early onset adult MG, was shown to be a risk allele in the postpubertal onset JMG group.
List of papers
|Paper I: Popperud TH, Boldingh MI, Brunborg C, Faiz KW, Heldal AT, Maniaol AH, et al. Juvenile myasthenia gravis in Norway: A nationwide epidemiological study. Eur J Paediatr Neurol. 2017;21(2):312-7. DOI:10.1016/j.ejpn.2016.09.001. The article is included in the thesis. Also available at https://doi.org/10.1016/j.ejpn.2016.09.001|
|Paper II: Popperud TH, Boldingh MI, Rasmussen M, Kerty E. Juvenile myasthenia gravis in Norway: Clinical characteristics, treatment, and long-term outcome in a nationwide population-based cohort. Eur J Paediatr Neurol. 2017;21(5):707-14. DOI:10.1016/j.ejpn.2017.04.003. The article is included in the thesis. Also available at https://doi.org/10.1016/j.ejpn.2017.04.003|
|Paper III: Popperud TH, Viken MK, Kerty E, Lie BA. Juvenile myasthenia gravis in Norway: HLA-DRB1*04:04 is positively associated with prepubertal onset. PLoS ONE. 2017;12(10). DOI:10.1371/journal.pone.0186383. The article is included in the thesis. Also available at https://doi.org/10.1371/journal.pone.0186383|
|Paper IV: Popperud TH, Gul KA , Brunborg C , Olaussen RW, Abrahamsen TG, Osnes LT, Kerty E . Thymectomy in juvenile myasthenia gravis- any long term effect on immunosenescence markers? Submitted. To be published. The paper is not available in DUO awaiting publishing.|