738. Natural Killer Cell Dysfunction in HIV-Exposed Uninfected Infants
Session: Oral Abstract Session: The NICU and Beyond
Friday, October 9, 2015: 10:42 AM
Room: 32--ABC

Background: HIV-exposed uninfected infants (HEU) are a growing population. In the first year of life, HEU have higher rates of hospitalization and death due to lower respiratory tract infection (LRTI) and sepsis than HIV-unexposed infants (HUU). HEU and HUU have similar antibody responses to vaccines and presumably to infections, but cellular immune dysfunction may predispose HEU to infectious morbidity. We hypothesized that natural killer cells (NK) are impaired in HEU and may contribute to the development of LRTI morbidity.

Methods: Singleton, full-term infants were selected from an observational cohort of HIV-infected pregnancies in Latin America and the Caribbean. HUU with similar demographics were enrolled in Brazil.  Peripheral blood mononuclear cells (PBMC) from HEU and HUU were cryopreserved at birth and age 6 months. NK frequency, phenotype and function were assessed by flow cytometry with and without stimulation by K562 cells (human NK targets). Between-group differences were compared by Mann-Whitney tests with significance defined as p <0.05.

Results: The proportion of NK in PBMC was lower in 7 HEU vs. 13 HUU at birth (1.6% vs. 10.9%, p=0.001) and in 42 HEU vs. 39 HUU at 6 months (3.2% vs. 4.9%, p=0.004). K562-specific lysis was lower in HEU vs. HUU at 6 months (10.9% vs. 14.2%, p=0.002), but the difference was not seen after controlling for the proportion of NK in PBMC. Other measures demonstrating compromised NK function in HEU included: 1) K562-stimulated expression of IFNγ per cell was lower in HEU vs. HUU at birth (geometric mean fluorescence=810 vs. 1603, p=0.003) and 6 months (1995 vs. 2217, p=0.016); 2) the proportion of NK that upregulated IFNγ after K562 stimulation was lower in HEU vs. HUU at birth and 6 months (Fig); 3) NK upregulation of perforin production after K562 stimulation was absent in HEU at birth but intact in HUU (Fig). There were no differences in perforin upregulation at 6 months or in K562-induced degranulation measured by CD107a cell membrane expression at birth or 6 months.

Conclusion: Compared with HUU, HEU had fewer and less functional NK at birth. Differences were attenuated but still present at 6 months. Further studies are needed to assess the association of NK dysfunction with development of LRTI.  

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Christiana Smith, MD1, Emilie Jalbert, MSc2, Volia De Almeida, MD3, Marisa Mussi-Pinhata, MD4, Rachel Cohen, MPH5, Qilu Yu, PhD5, Fabiana Amaral, MD4, Jorge Pinto, MD, DSc6, Jorge Alarcon, MD, MPH7, George Siberry, MD, MPH, FPIDS8, Adriana Weinberg, MD, FIDSA2 and NISDI-LILAC Protocol, (1)Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, (2)Pediatric Infectious Diseases, University of Colorado School of Medicine, Aurora, CO, (3)Federal University of Sao Carlos Biological and Health Sciences Center, Sao Carlos, Brazil, (4)University of Sao Paulo School of Medicine at Ribeirao Preto, Ribeirao Preto, Brazil, (5)Westat, Rockville, MD, (6)Federal University of Minas Gerais, Belo Horizonte, Brazil, (7)Epidemiology, D.A. Carrión Institute of Tropical Medicine, Lima, Peru, (8)Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD

Disclosures:

C. Smith, None

E. Jalbert, None

V. De Almeida, None

M. Mussi-Pinhata, None

R. Cohen, None

Q. Yu, None

F. Amaral, None

J. Pinto, None

J. Alarcon, None

G. Siberry, None

A. Weinberg, None

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