title: Concurrent HLA-related response factors mediate recombinant hepatitis B vaccine major adverse events.
abstract: Recombinant hepatitis B (HB) vaccines have successfully reduced infection, cirrhosis and carcinoma, but questions have endured about causality of serious adverse events following vaccination. After an event in a pediatric patient an investigation reviewed HLA vaccine response effects and analyzed genetics in reported cases. There are apparent common causal immune mechanisms among reported adverse events. HLA class II alleles/haplotypes linked to HB vaccine cellular/non-response and Crohn's disease can create conditions that actively/passively amplify, respectively, all or other components of the immune response to the HB vaccine. Presence of the HLA class I allele A2 can result in heavy cytotoxic T-cell activation and vaccine/self-peptide presentation to immune cells. If HLA autoimmune susceptibility alleles/haplotypes are present that control other immune response components, the probability is elevated that these will activate cross-reactive immune cells; the cells, their inflammatory secretions and/or auto-antibodies may initiate adverse events reflecting those susceptibilities. Probable DRB1 amplifying alleles are noted. High-resolution DNA typing and results analysis are described to test the hypothesis in known HB vaccine adverse event patients. Possible practical applications stemming from hypothesis validation are described.
authors.affiliation: Greater Portland Pediatric Associates, Maine Medical Center, Portland, ME, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Miller
authors.forename: L H
authors.initials: LH
authors.lastname: Whitehair
mesh_terms: D000483:Alleles; D002648:Child; D003424:Crohn Disease / Q000139:chemically induced / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006684:HLA-DR Antigens; D006509:Hepatitis B / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000009:adverse effects*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male
chemical_list: D006680:HLA Antigens; D006684:HLA-DR Antigens; D017325:Hepatitis B Vaccines; D015395:Histocompatibility Antigens Class I