title: Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity.
abstract: The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.
authors.affiliation: Immunovirology, University of Antioquia, Medellín, Colombia. vibe@elhospital.org.co
authors.forename: Victoria Inés
authors.initials: VI
authors.lastname: Bedoya
authors.forename: Fabian Alberto
authors.initials: FA
authors.lastname: Jaimes
authors.forename: Julio C
authors.initials: JC
authors.lastname: Delgado
authors.forename: Claudia
authors.initials: C
authors.lastname: Rugeles
authors.forename: Xiomara
authors.initials: X
authors.lastname: Usuga
authors.forename: Wildeman
authors.initials: W
authors.lastname: Zapata
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Castaño
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
authors.forename: Gene
authors.initials: G
authors.lastname: Shearer
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Rugeles
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D054502:Histocompatibility, Maternal-Fetal / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D007519:Isoantigens / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology; D012260:Ribonucleases / Q000378:metabolism* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007519:Isoantigens; D012260:Ribonucleases