title: Human leukocyte antigen genotypes in the genetic control of adaptive immune responses to smallpox vaccine.
abstract: BACKGROUND
  The role of human leukocyte antigen (HLA) genes in mediating adaptive immune responses to smallpox vaccine remains unknown.
  
  
  METHODS
  We determined genotypes for a group of individuals (n = 1071) who received a single dose of smallpox vaccine (Dryvax, Wyeth Laboratories) and examined associations between HLA alleles and 15 immune outcomes to smallpox vaccine on a per-locus and a per-allele level.
  
  
  RESULTS
  We found significant associations between the HLA-B and HLA - DQB1 loci and vaccinia-induced antibodies (P = .04 for each locus), with the HLA-B*1302 (P = .036), B*3802 (P = .011), DQB1*0302 (P = .015), and DQB1*0604 (P = .017) alleles being associated with higher levels. Significant global associations were identified between vaccinia-specific interferon (IFN)-γ and DQA1 (P = .003), interleukin (IL)-1β and HLA-B (P = .004), tumor necrosis factor (TNF)-α and HLA-B (P = .006), and IL-6 and HLA-B locus (P = .016) for secreted cytokines, as well as between CD8α(+) IFN-γ Elispot responses and DQB1 (P = .027). Subjects carrying B*3906 (P = .006) and B*5701 (P < .001) secreted higher levels of IL-1β than did subjects who did not carry these alleles. Subjects carrying the B*5301 (P = .047) and B*5601 (P = .008) alleles secreted less IL-1β, compared with subjects who did not carry these alleles. The B*3502 (P = .009), B*5601 (P = .004), and B*5701 (P < .001) alleles were significantly associated with variations in TNF-α secretion.
  
  
  CONCLUSIONS
  These data suggest that variations in antibody and cellular IFN-γ, IL-1β, TNF-α, and IL-6 immune responses after receipt of smallpox vaccine are genetically controlled by HLA genes or genes in close linkage disequilibrium to these alleles.
authors: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors: Inna G
authors: IG
authors: Ovsyannikova
authors: Robert A
authors: RA
authors: Vierkant
authors: V Shane
authors: VS
authors: Pankratz
authors: Robert M
authors: RM
authors: Jacobson
authors: Gregory A
authors: GA
authors: Poland
references: J Immunol. 2000 Oct 15;165(8):4748-55
references: 11035120
references: J Infect Dis. 2007 Jul 15;196(2):212-9
references: 17570108
references: Immunol Allergy Clin North Am. 2003 Nov;23(4):731-43
references: 14753389
references: Curr Opin Immunol. 2009 Jun;21(3):314-20
references: 19524427
references: J Infect Dis. 2006 Aug 15;194(4):444-53
references: 16845627
references: Pediatrics. 2008 May;121(5):e1091-9
references: 18450852
references: Immunogenetics. 2005 Feb;56(11):798-807
references: 15712014
references: MMWR Recomm Rep. 2001 Jun 22;50(RR-10):1-25; quiz CE1-7
references: 15580803
references: Clin Vaccine Immunol. 2007 Feb;14(2):115-22
references: 17215337
references: Scand J Clin Lab Invest. 2005;65(8):681-9
references: 16319042
references: J Infect Dis. 2004 May 1;189(9):1696-704
references: 15116308
references: Tissue Antigens. 2009 Nov;74(5):373-85
references: 19765261
references: FEMS Immunol Med Microbiol. 2004 Sep 1;42(1):48-52
references: 15325397
references: Clin Pharmacol Ther. 2007 Dec;82(6):653-64
references: 17971814
references: Vaccine. 2002 Jun 7;20(19-20):2597-602
references: 12057618
references: Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2709-14
references: 10694578
references: J Infect Dis. 2004 Oct 1;190(7):1286-94
references: 15346340
references: Nat Genet. 1997 Sep;17(1):11-2
references: 9288086
references: J Infect Dis. 2008 Jul 1;198(1):16-22
references: 18454680
references: J Infect Dis. 2010 Apr 15;201(8):1141-9
references: 20205591
references: Bull World Health Organ. 1975;52(3):307-11
references: 1084801
references: Hepatology. 2004 Apr;39(4):978-88
references: 15057902
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13980-5
references: 16172378
references: J Virol. 2004 Apr;78(8):3811-6
references: 15047796
references: J Infect Dis. 2006 Aug 15;194(4):435-43
references: 16845626
references: J Immunol Methods. 2009 Feb 28;341(1-2):97-105
references: 19038260
references: Clin Vaccine Immunol. 2009 Aug;16(8):1105-12
references: 19535540
references: Immunogenetics. 2005 Dec;57(11):828-36
references: 16331510
references: J Infect Dis. 2003 Aug 1;188(3):440-8
references: 12870127
references: Vaccine. 1999 Jan 28;17(4):330-9
references: 9987171
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references: 12883005
references: Vaccine. 2009 May 26;27(25-26):3319-23
references: 19200827
references: JAMA. 2004 Sep 8;292(10):1205-12
references: 15353533
references: Lancet. 2005 Oct 8;366(9493):1315-23
references: 16214603
references: Hum Genet. 2009 Nov;126(5):685-96
references: 19597844
references: Vaccine. 2009 May 26;27(25-26):3359-66
references: 19200845
references: J Infect Dis. 2002 Jul 1;186(1):106-9
references: 12089669
references: AIDS. 2002 Nov 22;16(17):2275-84
references: 12441799
references: N Engl J Med. 2002 Apr 25;346(17):1275-80
references: 11923489
references: Vaccine. 2008 Sep 12;26 Suppl 4:D35-40
references: 19230157
references: Lancet. 2005 Jan 29-Feb 4;365(9457):362-3
references: 15680437
references: J Virol. 2001 Sep;75(18):8681-9
references: 11507213
references: J Infect Dis. 2006 Mar 1;193(5):655-63
references: 16453260