title: HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission.
abstract: HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83). Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child) significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642). However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children's DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV.
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
authors.forename: Ma
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Embree
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Suzie
authors.initials: S
authors.lastname: Ramdahin
authors.affiliation: National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bielawny
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Tyler
authors.initials: T
authors.lastname: Laycock
authors.affiliation: National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Tuff
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Darren
authors.initials: D
authors.lastname: Haber
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Mariel
authors.initials: M
authors.lastname: Plummer
authors.affiliation: Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada; National Microbiology Laboratory, Winnipeg, Manitoba, Canada.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Plummer
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000635:transmission*; D015497:HIV-1; D059811:HLA-DRB1 Chains / Q000235:genetics; D059826:HLA-DRB3 Chains / Q000235:genetics; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007630:Kenya; D008297:Male; D011247:Pregnancy; D012307:Risk Factors; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen; D059826:HLA-DRB3 Chains; D000949:Histocompatibility Antigens Class II