BACKGROUND/AIMS: 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.
RCT Entities:
BACKGROUND/AIMS: 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: Martin R Weihrauch; Michael von Bergwelt-Baildon; Milos Kandic; Martin Weskott; Winfried Klamp; Joachim Rosler; Joachim L Schultze Journal: World J Gastroenterol Date: 2008-04-28 Impact factor: 5.742
Authors: Michael Osthoff; Elizabeth Irungu; Kenneth Ngure; Nelly Mugo; Katherine K Thomas; Jared M Baeten; Damon P Eisen Journal: Vaccine Date: 2014-07-10 Impact factor: 3.641
Authors: Jonathan P Moorman; Chun L Zhang; Lei Ni; Cheng J Ma; Ying Zhang; Xiao Y Wu; Penny Thayer; Tareq M Islam; Thomas Borthwick; Zhi Q Yao Journal: Vaccine Date: 2011-03-03 Impact factor: 3.641
Authors: Alexander J Mentzer; Daniel O'Connor; Andrew J Pollard; Adrian V S Hill Journal: Philos Trans R Soc Lond B Biol Sci Date: 2015-06-19 Impact factor: 6.237
Authors: Jia M Wang; Cheng J Ma; Guang Y Li; Xiao Y Wu; Penny Thayer; Pamela Greer; Ashley M Smith; Kevin P High; Jonathan P Moorman; Zhi Q Yao Journal: Vaccine Date: 2013-03-14 Impact factor: 3.641