Genetiske risikofaktorer hos pasienter med narkolepsi etter svineinfluensavaksine

I denne studien har forskere ved Nasjonalt kompetansesenter for nevroutviklingsforstyrrelser og hypersomnier (NevSom), Universitetet i Oslo og Oslo universitetssykehus undersøkt om pasienter som fikk påvist narkolepsi etter svineinfluensa-vaksineringen hadde genetiske risikofaktorer som lignet det man tidligere har sett hos narkolepsipasienter. I tillegg til at forskerne fant risikofaktorer som hos narkolepsipasienter, fant de også nye risikofaktorer.
Resultatene av denne studien tyder på at sykdomsmekanismen bak narkolepsi er uavhengig av om man har fått svineinfluensavaksine, eller ikke.

HLA and sleep parameter associations in post-H1N1 narcolepsy type 1 patients and first-degree relatives

Hilde T. Juvodden, Marte K. Viken, Sebjørg E. H. Nordstrand, Rannveig Viste,  Lars T. Westlye, Per M. Thorsby, Benedicte A. Li, Stine Knudsen-Heier

Studien er publisert i SLEEP

STUDY OBJECTIVES: To explore HLA (human leukocyte antigen) in post-H1N1 narcolepsy type 1 patients (NT1), first-degree relatives and healthy controls, and assess HLA associations with clinical and sleep parameters in patients and first-degree relatives.
METHODS: Ninety post-H1N1 NT1 patients and 202 of their first-degree relatives were HLA-genotyped (next generation sequencing) and phenotyped (semi-structured interviews, Stanford Sleep Questionnaire, polysomnography, multiple sleep latency test). HLA allele distributions were compared between DQB1*06:02-heterozygous individuals (77 patients, 59 parents, 1230 controls). A subsample (74 patients, 114 relatives) was investigated for associations between HLA-loci and continuous sleep variables using logistic regression. Identified candidate HLA-loci were explored for HLA allele associations with hypnagogic hallucinations and sleep paralysis in 90 patients, and patient allele findings were checked for similar associations in 202 relatives.
RESULTS: DQB1*06:02 heterozygous post-H1N1 NT1 patients (84.4% H1N1-vaccinated), showed several significant HLA associations similar to those reported previously in samples of mainly sporadic NT1 i.e. DQB1*03:01, DRB1*04:01, DRB1*04:02, DRB1*04:07, DRB1*11:04, A*25:01, B*35:03 and B*51:01, and novel associations i.e. B*14:02, C*01:02 and C*07:01. Parents HLA alleles did not deviate significantly from controls. The HLA-C locus was associated with sleep parameters in patients and relatives. In patients C*02:02 seems to be associated with protective effects against sleep paralysis and hypnagogic hallucinations.
CONCLUSION: Our findings of similar risk/protective HLA-alleles in post-H1N1 as in previous studies of mainly sporadic narcolepsy support similar disease mechanisms. We also report novel allelic associations. Associations between HLA-C and sleep parameters were seen independent of NT1 diagnosis, supporting involvement of HLA-C in sleep subphenotypes.