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Expression data from HIV exposed and uninfected women

ABSTRACT: We carried out a global whole blood genome wide expression profiling of HIV exposed and uninfected women from Nairobi to identify host factors which may be a key contribution to HIV resistance phenomenon. To identify novel biomarkers for HIV resistance including pathways that may be critical in anti-HIV vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV Exposed and uninfected volunteers from a commercial sex worker cohort in Nairobi and compared their profiles to HIV susceptible negative controls. Whole blood samples were collected from 43 HIV resistant and a similar number of HIV negative antenatal clinic attendees and total RNA extracted and hybridized to the affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). More than 2,274 probe sets were differentially expressed in the HIV resistant women as compared to the control group (fold change ≥1.3; p value ≤ 0.0001, FDR <0.05) . Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished EUs from susceptible controls. Pathway analysis of the differentially expressed genes through the KEGG signaling revealed a majority of the impacted pathways (13 of 15, 87%) were significantly down expressed. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, Phosphatidyl inositol, Natural Killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up expressed. We infer that the hallmark of HIV resistance is down regulation of genes in key signaling pathways that HIV depends on for infection and suggest that an anti-HIV vaccine design may need to incorporate components that switch down specific immune activating factors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33580 | GEO | 2012/11/11

SECONDARY ACCESSION(S): PRJNA148577

REPOSITORIES: GEO

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Project description:The transplacental transfer of maternal IgG to the developing fetus is critical for infant protection against infectious pathogens in the first year of life. However, factors that modulate the transplacental transfer efficiency of maternal IgG that could be harnessed for maternal vaccine design remain largely undefined. HIV-infected women have impaired placental IgG transfer, yet the mechanism underlying this impaired transfer is unknown, presenting an opportunity to explore factors that contribute to the efficiency of placental IgG transfer. We measured the transplacental transfer efficiency of maternal HIV and other pathogen-specific IgG in historical U.S. (n=120) and Malawian (n=47) cohorts of HIV-infected mothers and their HIV58 exposed uninfected and HIV-infected infants. We then examined the role of maternal HIV disease progression, infant factors, placental Fc receptor expression, and IgG Fc region subclass and glycan signatures and their association with transplacental transfer efficiency of maternal antigen-specific IgG. We established 3 distinct phenotypes of placental IgG transfer efficiency in HIV-infected women, including: 1) efficient transfer of the majority of antigen-specific IgG populations; 2) generally poor IgG transfer phenotype that was strongly associated with maternal CD4+ T cell counts, hypergammaglobulinemia, and frequently yielded non-protective levels of vaccine-specific IgG; and 3) variable transfer of IgG across distinct antigen specificities. Interestingly, maternal IgG characteristics, such as binding to placentally expressed Fc receptors FcgRIIa and FcgRIIIa, IgG subclass frequency, and Fc region glycan profiles were associated with placental IgG transfer efficiency. These maternal IgG transplacental transfer determinants were distinct among different antigen-specific IgG populations. Our findings suggest that in HIV-infected women, both maternal disease progression and Fc region characteristics modulate the selective placental transfer of distinct IgG subpopulations, with implications for both the health of HIV-exposed uninfected infants and maternal vaccine design.

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Expression data from HIV exposed and uninfected women

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