Povezanost primjene cjepiva Pandemrix i incidencije narkolepsije tipa 1 s obzirom na učestalost alelne varijante HLA-DQB1*06:02

master's thesis

• Title (english): Association between the use of the Pandemrix vaccine and the incidence of narcolepsy type 1 with regard to the HLA-DQB1*06:02 allele frequency
• Author: Ivana Karuc
• Mentor: Anita Somborac Bačura (mentor)
• Committee member: Anita Somborac Bačura (predsjednik povjerenstva)
• Committee member: Sandra Šupraha-Goreta (član povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2024-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Narkolepsija tipa 1 (NT1) je poremećaj spavanja koji nastaje zbog kronične deficijencije oreksina do koje dolazi zbog selektivnog imunoposredovanog uništenja oreksinskih neurona u hipotalamusu. Osim disregulacije ciklusa spavanje - budnost, bolest se prezentira raznim motoričkim, kognitivnim, psihijatrijskim, metaboličkim i autonomnim simptomima, a najspecifičniji simptom je katapleksija. Etiologija je multifaktorijalna, a uključuje genske, epigenske i okolišne čimbenike. Rizični faktori su pozitivnost na HLA-DQB1*06:02 alelnu varijantu, prethodna infekcija virusom influence H1N1 ili Streptococcus-om te primjena cjepiva protiv influence A H1N1/pdm09 s AS03 adjuvansom (Pandemrix). Patofiziologija bolesti još uvijek je tema istraživanja, no do sad utvrđeni genetički, epidemiološki i eksperimentalni podatci podržavaju hipotezu da je NT1 autoimuna bolest posredovana T-limfocitima usmjerena na oreksinske neurone. Razumijevanje imunopatogeneze NT1 važno je iz javnozdravstvene perspektive jer može usmjeriti daljnja istraživanja u smjeru novih terapijskih mogućnosti narkolepsije i drugih autoimunih bolesti te pomoći uspostaviti globalno koordiniranu mrežu ispitivanja sigurnosti cjepiva kao ključnog čimbenika u borbi protiv budućih pandemija.

Abstract (english)

Narcolepsy type 1 (NT1) is a sleep disorder caused by chronic orexin deficiency that occurs due to selective immune-mediated destruction of orexin neurons in the hypothalamus. In addition to dysregulation of the sleep-wake cycle, the disease presents itself with various motor, cognitive, psychiatric, metabolic, and autonomic symptoms, the most specific symptom being cataplexy. The etiology is multifactorial and includes genetic, epigenetic, and environmental factors. Risk factors include HLA-DQB1*06:02-positivity, previous H1N1 influenza virus or Streptococcus infection, and administration of the AS03-adjuvanted influenza A H1N1/pdm09 vaccine (Pandemrix). The pathophysiology of the disease is still an object of ongoing research, but the genetic, epidemiological, and experimental data established so far support the hypothesis that NT1 is a T-lymphocyte-mediated autoimmune disease targeting orexin-producing neurons. Understanding the immunopathogenesis of NT1 is important from the perspective of public health because it can guide further research toward modern therapeutic approaches to narcolepsy and other autoimmune diseases and also help establish a globally coordinated vaccine safety infrastructure as a crucial factor in the fight against future pandemics.

• Keywords: narkolepsija; Pandemrix; H1N1; influenca; HLA-DQB1*06:02; oreksin; hipokretin
• Keywords (english): narcolepsy; Pandemrix; H1N1; influenza; HLA-DQB1*06:02; orexin; hypocretin
• Language: croatian
• URN:NBN: urn:nbn:hr:163:317986
• Study programme: Title: Medical biochemistry - integrated undergraduate and graduate - university study; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: sveučilišni magistar medicinske biokemije i laboratorijske medicine (sveučilišni magistar medicinske biokemije i laboratorijske medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-09-25 13:13:02