The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction.
The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA- along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value<0.05) with TRA as well as suggestive (P-value<0.1) associations with P2RY11 and CTSH were found. These associations suggest a very strong gene-environment interaction, in which the influenza A(H1N1)pdm09 strain or Pandemrix vaccine can act as potent environmental triggers.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
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Bomfim
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Lamb
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
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Fink
Department of Pediatrics, Halmstad County Hospital, Halmstad, Sweden.
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Szakács
Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.|Cardiovascular Medicine Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden.
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Silveira
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
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Franzén
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
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Azhary
Division of Therapeutic Immunology, Department of Laboratory Medicine, Stockholm, Sweden.|Center for Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital, Stockholm, Sweden.
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Maeurer
Medical Products Agency, Uppsala, Sweden.
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Feltelius
Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Darin
Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Hallböök
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Arnheim-Dahlström
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
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Kockum
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.|Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
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Olsson
D059647:Gene-Environment Interaction; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000009:adverse effects*; D009290:Narcolepsy / Q000139:chemically induced* / Q000235:genetics*; D012189:Retrospective Studies
D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007252:Influenza Vaccines; C556153:pandemrix