title: C4A deficiency and nonresponse to hepatitis B vaccination.
abstract: OBJECTIVE
  Hepatitis B vaccination failure has been linked to the presence of certain human leukocyte antigen class II alleles. However, the functional background of these associations has remained unclear. Complement component C 4 is encoded within the major histocompatibility complex and is essential for classical pathway activation.
  
  
  METHODS
  Healthy individuals (n=4269) were vaccinated in a prospective trial with Engerix B. Nonresponse was classified as anti-HBs<10 U/l after the last vaccination. Seventy-three nonresponders (NR) (1.7%) were identified. For comparison 53 responders (R) (anti-HBs>10 IU/l) were drawn randomly from the same cohort. C4 allotyping was carried out by high-voltage agarose gel electrophoresis and C4alpha-chain typing using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. C4 gene deletions (C4Del) were studied by Southern blot.
  
  
  RESULTS
  C4AQ0 alleles were observed in 45/73 (62%) NR compared to 17/53 (32%) R (P=0.001). C4ADel was observed in 24/73 (33%) NR and in 6/52 (12%) R (P=0.006). C4AQO alleles were present in 21/49 (43%) NR without C4Del compared to 10/46 (22%) in R without C4Del (P=0.031). In a logistic regression with DRB1*0301, DRB1*07, DRB1*1301 and C4AQ0 all except for DRB1*0301 showed a significant association.
  
  
  CONCLUSIONS
  C4AQ0 shows a DRB1*0301 independent association with vaccine failure. C4AQ0 alleles probably contribute to inefficient complement activation and failure of B cells to secrete anti-HBs.
authors.affiliation: I. Department of Internal Medicine, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, Mainz, Germany. hoehler@mail.uni-mainz.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Höhler
authors.forename: Beate
authors.initials: B
authors.lastname: Stradmann-Bellinghausen
authors.forename: Roland
authors.initials: R
authors.lastname: Starke
authors.forename: Roland
authors.initials: R
authors.lastname: Sänger
authors.forename: Anja
authors.initials: A
authors.lastname: Victor
authors.forename: Christian
authors.initials: C
authors.lastname: Rittner
authors.forename: Peter M
authors.initials: PM
authors.lastname: Schneider
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D015934:Complement C4a / Q000235:genetics* / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006509:Hepatitis B / Q000453:epidemiology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016036:Seroepidemiologic Studies; D017211:Treatment Failure
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines; D015934:Complement C4a