title: Overall conceptual framework for studying the genetics of autoimmune diseases following vaccination: a regulatory perspective.
abstract: The US Vaccine Adverse Event Reporting System contains case reports of autoimmune diseases (ADs) occurring following vaccinations. ADs are rare and occur in unvaccinated people, making the potential association between vaccines and ADs challenging to evaluate. Developing mechanistic pathways that link genes, immune mediators, vaccine components and ADs would be helpful for hypothesis generation, enhancing theories of biologic plausibility and grouping rare autoimmune adverse events to increase the ability to detect and evaluate safety signals. Here, we propose a conceptual framework for investigating the genetics of ADs as safety signals following vaccination, potentially contributing to the identification of relevant biomarkers. We also discuss a study design that incorporates genetic information into postmarket clinical evaluation of autoimmune adverse events following vaccination.
authors.affiliation: Office of Biostatistics & Epidemiology, Center for Biologics Evaluation & Research, US Food & Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Lababidi
authors.affiliation: Johns Hopkins University, School of Public Health, Baltimore MD, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sutherland
authors.affiliation: Division of Biostatistics, Office of Biostatistics & Epidemiology, Center for Biologics Evaluation & Research, US Food & Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Krasnicka
authors.affiliation: Office of Biostatistics & Epidemiology, Center for Biologics Evaluation & Research, US Food & Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Forshee
authors.affiliation: Office of Biostatistics & Epidemiology, Center for Biologics Evaluation & Research, US Food & Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Anderson
mesh_terms: D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D033161:Government Regulation; D006801:Humans; D011358:Product Surveillance, Postmarketing; D012449:Safety; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence; D014611:Vaccination / Q000009:adverse effects* / Q000331:legislation & jurisprudence*
chemical_list: D015415:Biomarkers
keywords: biologic plausibility; genetics of autoimmune diseases; molecular biomarkers; rare adverse events; vaccine safety; vaccinomics