title: Elevated concentrations of milk β2-microglobulin are associated with increased risk of breastfeeding transmission of HIV-1 (Vertical Transmission Study).
abstract: There is increasing evidence to support a relationship between human immunodeficiency virus (HIV-1) transmission through breastfeeding and milk host factors. We analyzed skim milk proteome to further determine the contribution of host factors to the risk of mother-to-child transmission of HIV-1. Quantitative mass spectrometry analysis was performed on nine case-control pairs of HIV+ transmitter/nontransmitter mothers, and specific biochemical assays on two selected proteins were assessed in an independent validation set of 127 samples. 33 identified proteins were differentially expressed between HIV+ transmitter and nontransmitter mothers. Among them, β2-microglobulin was significantly higher in the maternal transmitter than in the nontransmitter groups (p value = 0.0007), and S100A9 was significantly higher in the early maternal transmitter cases (before 4 months of age) compared with the nontransmitters (p value = 0.004). β2-Microglobulin correlated with milk and plasma HIV viral load and CD4+ cell count, whereas S100A9 correlated with the estimated timing of infection of the infant through breastfeeding. Finally, β2-microglobulin concentration in milk could accurately predict the risk of HIV-1 postnatal transmission by breastfeeding (p value < 0.0001, log-rank test). In conclusion, milk β2-microglobulin and S100A9 are host factors that are found to be associated with mother-to-child transmission of HIV-1.
authors.affiliation: University of Montpellier 1 , EA 2415, 641 av. du Doyen Gaston Giraud, 34093 Montpellier, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Mangé
authors.forename: Edouard
authors.initials: E
authors.lastname: Tuaillon
authors.forename: Johannes
authors.initials: J
authors.lastname: Viljoen
authors.forename: Nicolas
authors.initials: N
authors.lastname: Nagot
authors.forename: Sophie
authors.initials: S
authors.lastname: Bendriss
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Bland
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Newell
authors.forename: Philippe
authors.initials: P
authors.lastname: Van de Perre
authors.forename: Jérôme
authors.initials: J
authors.lastname: Solassol
mesh_terms: D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D040502:Calgranulin B / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000235:genetics / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000737:chemistry / Q000821:virology*; D058977:Molecular Sequence Annotation; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis*; D013019:South Africa; D019562:Viral Load; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D040502:Calgranulin B; D020543:Proteome; D012367:RNA, Viral; D001613:beta 2-Microglobulin