Mother‐Child Class I HLA Concordance Increases Perinatal Human Immunodeficiency Virus Type 1 Transmission

Abstract

Major histocompatibility complex (MHC) gene products are expressed on human immunodeficiency virus (HIV)-infected cells and incorporated into the lipid envelope of HIV virions. Macaques immunized with human MHC gene products are protected from simian immunodeficiency virus challenge when the virus is grown in cells expressing the same MHC alleles. To relate these findings to mother-to-child transmission of HIV-1, investigations of whether sharing HLA between mother and infant influenced the risk of transmission of HIV-1 to the child were carried out. Class I HLA concordance was independently associated with a stepwise increase in the risk of perinatal HIV-1 transmission for each additional concordant allele (odds ratio, 2.63; 95% confidence interval, 1.36-5.07; P = .003). Thus, discordant HLA may provide infants with a means of protection against HIV-1 as a result of allogeneic infant anti-maternal MHC immune responses.

Human Leukocyte Antigen (HLA) B*18 and Protection against Mother-to-Child HIV Type 1 Transmission

“…7 The relationship between the A2 supertype and risk of vertical transmission was independent of the protective effect of HLA discordance between mother and child. 6,8 We examined associations between mother-to-child HIV-1 transmission and frequently expressed HLA alleles in a Kenyan perinatal cohort. Special attention was given to defining early and late transmission events to determine effects of HLA on HIV-1 acquisition among breast-feeding infants in sub-Saharan Africa.…”

Immunité maternelle et transmission mère-enfant du VIH et du VHC

“…Comparées aux mères qui ne transmettent pas le virus, les activités cytotoxiques et suppressives des lymphocytes T CD8 + anti-VIH sont réduites chez les mères qui le transmettent [21], bien que les variants VIH qui sont préférentiellement transmis à l'enfant soient ceux-là même qui échappent à la réponse cellulaire maternelle [22] et aux anticorps neutralisants [23]. On pense également que des facteurs génétiques associés à la réponse immunitaire, notamment la présence de l'allèle HLA-DR13, ainsi que la discordance entre les HLA de classe I de la mère et du foetus protègeraient ce dernier contre la TME du VIH [24]. Enfin, des réponses T cytotoxiques [25] et des perturbations du répertoire immunitaire apparentées à des réponses antigène-spécifiques [26,27] ont été observées chez des enfants non infectés nés de mères infectées.…”

Host-Pathogen Interactions in Emerging and Re-emerging Infectious Diseases: A Genomic Perspective of Tuberculosis, Malaria, Human Immunodeficiency Virus Infection, Hepatitis B, and Cholera

“…The absence of this CCR5 variant in most African and Asian populations and its low prevalence (∼5%) in African Americans suggest that its protective effect against HIV transmission may be limited to Caucasians. HLA class I genes are also important, because HLA discordance was found to reduce vertical HIV transmission by one third in one mother-infant study in Kenya (80). Blood group types, such as Lewis antigen, may influence transmission through mucosal routes (16).…”