Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity 英文参考文献.docVIP

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Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity 英文参考文献.doc

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Extended LTA, TNF, LST1 and HLA Gene Haplotypes and Their Association with Rubella Vaccine-Induced Immunity 英文参考文献

ExtendedLTA,TNF,LST1andHLAGeneHaplotypesand TheirAssociationwithRubellaVaccine-Induced Immunity InnaG.Ovsyannikova1,4*,RobertA.Vierkant3,V.ShanePankratz3,RobertM.Jacobson1,2,GregoryA. Poland1,2,4 * 1Vaccine Research Group, Mayo Clinic, Rochester, Minnesota, United States of America, 2Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota,UnitedStatesofAmerica,3DepartmentofHealthSciencesResearch,MayoClinic,Rochester,Minnesota,UnitedStatesofAmerica,4PrograminTranslational ImmunovirologyandBiodefense,MayoClinic,Rochester,Minnesota,UnitedStatesofAmerica Abstract Background: Recent studies have suggested the importance of HLA genes in determining immune responses following rubellavaccine.ThetelomericclassIIIregionoftheHLAcomplexharborsseveralgenes,includinglymphotoxinalpha(LTA), tumornecrosisfactor(TNF)andleukocytespecifictranscript-1(LST1)genes,locatedbetweentheclassIBandclassIIDRB1 loci.ApartfromHLA,littleisknownabouttheeffectofthisextendedgeneticregiononHLAhaplotypicbackgroundsas appliedtoimmuneresponses. Methodology/PrincipalFindings:WeexaminedtheassociationbetweenimmuneresponsesandextendedclassI-classII- classIIIhaplotypesamong714healthychildrenaftertwodosesofrubellavaccination.Theseextendedhaplotypeswere thencomparedtotheHLA-onlyhaplotypes.Themostsignificantassociationwasobservedbetweenhaplotypesextending acrosstheHLAclassIregion,ten-SNPhaplotypes,andtheHLAclassIIregion(i.e.A-C-B-LTA-TNF-LST1-DRB1-DQA1-DQB1- DPA1-DPB1)andrubella-specificantibodies(globalp-valueof0.03).AssociationswerefoundbetweenbothextendedA*02- C*03-B*15-AAAACGGGGC-DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 (p=0.002) and HLA-only A*02-C*03-B*15- DRB1*04-DQA1*03-DQB1*03-DPA1*01-DPB1*04 haplotypes(p=0.009)andhigherlevelsofrubellaantibodies.TheclassII HLA-only haplotype DRB1*13-DQA1*01-DQB1*06-DPA1*01-DPB1*04 (p=0.04) lacking LTA-TNF-LST1 SNPs was associated withlowerrubellaantibodyresponses.Similarly,theclassI-classIIHLA-onlyA*01-C*07-B*08-DRB1*03-DQA1*05-DQB1*02- DPA1*01