Whitney HarringtonSeattle Children’s Research Institute · Department of Pediatrics
Whitney Harrington
MD PhD
About
47
Publications
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Introduction
Additional affiliations
July 2018 - present
July 2018 - present
July 2014 - June 2018
Publications
Publications (47)
Infants exposed to HIV but uninfected (iHEU) display altered cellular immunity and are at increased risk of infection through poorly understood mechanisms. We previously reported that iHEU have lower levels of maternal microchimerism (MMc), maternal cells transferred to the offspring in utero/during breastfeeding. We evaluated MMc levels in T cell...
T cells in the human female genital tract (FGT) are key mediators of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods require a healthcare pro...
T cells in the female genital tract (FGT) are a key mediator of susceptibility to and protection from infection, including HIV and other sexually transmitted infections. There is a critical need for increased understanding of the distribution and activation of T cell populations in the FGT, but current sampling methods are invasive and expensive, l...
Human breastmilk is rich in T cells; however, their specificity and function are largely unknown. We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector...
Biomedical personnel can become contaminated with nonhazardous reagents used in the laboratory. We describe molecular studies performed on nasal secretions collected longitudinally from asymptomatic laboratory coworkers to determine if they were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulating in the community...
Background
Asymptomatic and pre-symptomatic SARS-CoV-2 infections may contribute to ongoing community transmission, however, the benefit of routine screening of asymptomatic individuals in low-risk populations is unclear.
Methods
To identify SARS-CoV-2 infections 553 seronegative individuals were prospectively followed for 52 weeks. From 4/2020-7/...
Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed...
We compared the phenotype, diversity, and antigen specificity of T cells in the breastmilk and peripheral blood of lactating individuals who received SARS-CoV-2 mRNA vaccination. Relative to blood, breastmilk contained higher frequencies of T effector and central memory populations that expressed mucosal-homing markers. T cell receptor ( TCR ) sequ...
Rationale: SARS-CoV-2 gains entrance to airway epithelial cells (AECs) through binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) on the cell surface. However, ACE2 also converts angiotensin II into angiotensin-(1-7) and counterbalances the renin-angiotensin-aldosterone system, with resultant protective effects in the...
Background
Coronavirus disease 2019 (COVID-19) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor (AT1R-Ab).
Methods
We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or seve...
BACKGROUND
Coronavirus disease 2019 ( COVID-19 ) is associated with endothelial activation and coagulopathy, which may be related to pre-existing or infection-induced pro-thrombotic autoantibodies such as those targeting angiotensin II type I receptor ( AT1R-Ab ).
METHODS
We compared prevalence and levels of AT1R-Ab in COVID-19 cases with mild or...
Background:
Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during prim...
Background
Malaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking.
Methods
We characterized the relation...
The fate of protective immunity following mild SARS-CoV-2 infection remains ill defined. Here we characterize antibody responses in a cohort of participants recovered from mild SARS-CoV-2 infection with follow up to 6 months. We measure IgA, IgM, and IgG binding and avidity to viral antigens and assess neutralizing antibody responses over time. Fur...
Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors which influence MMc detection and level across infancy and the effect of MMc on T cell responses to BCG vaccination in a cohort of HIV exposed, uninfected and HIV unexposed...
Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was co...
We present a microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2). Plasma from 22 subjects who recovered from mild Coronavirus disease 2019 (COVID-19) and expressed anti-spike-trimer IgGs inhibited ACE2-spike binding to a greater degree than co...
High throughput serological tests that can establish the presence and functional activity of anti-SARS-COV2 antibodies are urgently needed. Here we present microsphere-based Flow Cytometry assays that quantify both anti-spike IgGs in plasma, and the ability of plasma to inhibit the binding of spike protein to angiotensin converting enzyme 2 (ACE2)....
Rapid generation of diagnostics is paramount to understand epidemiology and to control the spread of emerging infectious diseases such as COVID-19. Computational methods to predict serodiagnostic epitopes that are specific for the pathogen could help accelerate the development of new diagnostics. A systematic survey of 27 SARS-CoV-2 proteins was co...
Dried blood spots (DBS) are widely utilized as part of universal newborn screening and as a means of transporting samples from field sites. We use DBS from African field sites to assess for rare maternal-fetal cell exchange during pregnancy known as microchimerism. We aimed to develop a protocol to maximize the quantity of high-quality genomic DNA...
The live-attenuated varicella vaccine, a routine immunization in the United States since 1995, is both safe and effective. Like wild-type varicella-zoster virus, however, vaccine Oka (vOka) varicella can establish latency and reactivate as herpes zoster, rarely leading to serious disease, particularly among immunocompromised hosts. Previous cases o...
Objective:
To compare fetal microchimerism (FMc) in pregnancies with uncomplicated vaginal delivery (VD) versus Cesarean delivery (CD).
Design:
Prospective cohort study.
Setting:
University of Washington and Fred Hutchinson Cancer Research Center, USA.
Population:
Women delivering singleton pregnancies without pertinent antenatal complicatio...
Malaria in pregnancy remains one of the most important causes of adverse birth outcomes. In addition to the profoundly deleterious impact of maternal malaria on the health of the mother and fetus, malaria infection in pregnancy has been shown to affect the development of the fetal and infant immune system and may alter the risk of malaria and non‐m...
Importance
Identifying infectious causes of subacute or chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.
Objective
To present a case series of patients with diagnostically challenging subacute or chronic meningitis using metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) supported...
Importance: Identifying infectious causes of subacute and chronic meningitis can be challenging. Enhanced, unbiased diagnostic approaches are needed.
Objective: To present a case series of patients with diagnostically challenging subacute and chronic meningitis in whom metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF), supp...
Bidirectional transplacental exchange characterizes human pregnancy. Cells exchanged between mother and fetus can durably persist as microchimerism and may have both short- and long-term consequences for the recipient. The amount, type, and persistence of microchimerism are influenced by obstetric characteristics, pregnancy complications, exposures...
Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-versus-leukemia are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this graft-versus...
Background:
A mother's infection with placental malaria (PM) can affect her child's susceptibility to malaria, although the mechanism remains unclear. The fetus acquires a small amount of maternal cells and DNA known as maternal microchimerism (MMc), and we hypothesized that PM increases MMc and that MMc alters risk of P. falciparum malaria during...
Objective: Risk and natural progression of coronary artery stenosis in Kawasaki Disease is not well-defined and is a potential cause of long term morbidity, despite treatment with IVIG. We present a novel study at a US tertiary pediatric care center identifying risk factors for stenosis.
Methods: We reviewed charts of all children that underwent ca...
Objective Despite treatment with intravenous immunoglobulin (IVIG), the natural progression to coronary artery stenosis in Kawasaki disease is not well defined and remains a potential cause of long-term morbidity. We present a novel study, at a US tertiary paediatric care centre, identifying risk factors for stenosis.
Methods We reviewed charts of...
Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerg...
Additional population genetic indices and fragment lengths of microsatellite loci for Independent lineages of highly sulfadoxine-resistant Plasmodium falciparum haplotypes, eastern Africa.
Severe malaria risk varies between individuals, and most of this variation remains unexplained. Here, we examined the hypothesis that cytokine profiles at birth reflect inter-individual differences that persist and influence malaria parasite density and disease severity throughout early childhood.
Cytokine levels (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, I...
In areas of widespread sulfadoxine-pyrimethamine resistance, intermittent treatment in pregnancy (IPTp) fails to prevent placental malaria (PM) and may exacerbate drug resistant infections. Because PM predicts increased susceptibility to parasitemia during infancy, we hypothesized that IPTp would also increase susceptibility to malaria infection an...
Millions of African women receive sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp) to avoid poor outcomes that result from malaria. However, parasites resistant to SP are widespread in parts of Africa, and IPTp may perversely exacerbate placental infections that contain SP-resistant parasites.
The study us...
Plasmodium falciparum-infected erythrocytes sequester in the placenta and elicit an inflammatory response that is harmful to both fetus and mother. Histologic measurements during placental malaria might provide surrogate end points for interventional trials, but existing histologic schemes capture limited complexity and are not consistently used am...
Intermittent preventive treatment in pregnancy (IPTp) is used to prevent Plasmodium falciparum malaria. However, parasites resistant to the IPTp drug sulfadoxine-pyrimethamine (SP) have emerged worldwide, and infections with mixed resistant and susceptible parasites are exacerbated by pyrimethamine in mice. In a prospective delivery cohort in Muhez...
Congenital malaria is rare and usually indolent but can be fatal. Mortality risk is high in newborns with Plasmodium falciparum born to nonimmune women, who typically present at birth or soon thereafter. Semi-immune women are less likely to transmit malaria, and their children often become ill weeks after delivery with less severe symptoms. Cases i...
Background
Despite recent advancements in HIV management, HIV-1-infected children in sub-Saharan Africa are still vulnerable to vaccine-preventable infections. When vaccinated, these children do not develop normal immune responses and thus may not develop protective immunity. It has previously been shown in HIV-1-infected adults that antibody titer...
Alternative splicing of mammalian transcripts, which yields many diverse protein products from one gene, is the rule and not the exception. Although the mechanisms that govern alternative splicing are being unraveled, little is known about the evolution of this critical engine of proteome diversity. Here we present a phylogenetic analysis from a se...
Questions
Question (1)
Hi -
We have single stranded genomic DNA from a Chelex-based extraction of dried blood spots. They are extracted into Tris (pH 10).
We would will be utilizing these samples for down stream qPCR within a few months time.
Is it better to leave them at 4 degrees or put them them at -20 but have to take them through a freeze thaw cycle?
I know dsDNA can be stored for long times at 4 degrees, but not sure about ssDNA. Should be long pieces, as genomic, not a cDNA library.
Thanks,
Whitney