title: Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation.
abstract: A number of large studies have demonstrated influenza vaccinations to be safe and effective. However, there have been some sporadic case reports, describing a temporal association of influenza vaccination with onset or relapse of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The nature of this association, beyond time of occurrence, remains unknown. The presentation of a previously healthy patient who developed ANCA-associated vasculitis (AAV) shortly after influenza vaccination provided us with the rare opportunity to study the possible mechanisms behind this observation. We tested the ability of different types and batches of influenza vaccines to stimulate proteinase-3 ANCA (PR3-ANCA) production in vitro. We found that only some influenza vaccines stimulated PR3-ANCA production in this patient. We demonstrated that this unusual response was associated with those vaccines that contained viral ribonucleic acid (RNA), the natural ligand for Toll-like receptor-7. Exome sequencing of the patient's DNA did not show any mutation in any of the molecules associated with Toll-like receptor signalling. We propose that hyper-reaction to viral RNA in the influenza vaccine may have contributed to the development of AAV following influenza vaccination in this patient.
authors.affiliation: Hanson Centre, Institute of Medical and Veterinary Science, Adelaide, Australia. lisa.jeffs@dhhs.tas.gov.au.|The University of Adelaide, Adelaide, Australia. lisa.jeffs@dhhs.tas.gov.au.|Royal Hobart Hospital, Level 4 Telstra Building 70 Collins Street, Hobart, TAS, 7000, Australia. lisa.jeffs@dhhs.tas.gov.au.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Jeffs
authors.affiliation: Hanson Centre, Institute of Medical and Veterinary Science, Adelaide, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: Nitschke
authors.affiliation: Department of Clinical and Experimental Immunology, University Maastricht, Maastricht, Netherlands.
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.affiliation: Hanson Centre, Institute of Medical and Veterinary Science, Adelaide, Australia.|The University of Adelaide, Adelaide, Australia.|Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Chen Au
authors.initials: CA
authors.lastname: Peh
authors.affiliation: Hanson Centre, Institute of Medical and Veterinary Science, Adelaide, Australia.|Department of Renal Medicine, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Plinio R
authors.initials: PR
authors.lastname: Hurtado
mesh_terms: D000328:Adult; D000368:Aged; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000209:etiology* / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015551:Autoimmunity; D016022:Case-Control Studies; D059472:Exome; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007252:Influenza Vaccines / Q000009:adverse effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053146:Myeloblastin / Q000276:immunology*; D012367:RNA, Viral / Q000032:analysis*; D012074:Remission Induction; D015398:Signal Transduction; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000235:genetics; D014611:Vaccination / Q000009:adverse effects
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007252:Influenza Vaccines; D008024:Ligands; D012367:RNA, Viral; C495345:TLR4 protein, human; C495348:TLR7 protein, human; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D053146:Myeloblastin
keywords: ANCA-associated vasculitis; Autoimmunity; Influenza vaccine; Innate immunity; RNA; TLR7