DR35 DataRelease
Release Date: 07/31/2020
| SDY1414: Alloantibodies in Pediatric Heart Transplantation (CTOTC-04) | |||||||
| Status: | New | ||||||
| Description: | There is currently a renewed interest in alloantibodies in transplantation. In 1966, Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells could cause hyperacute rejection of the renal allograft. Three years later, in a landmark study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific antibodies was highly predictive of acute graft failure. These observations led to the practice of performing prospective, donor-specific crossmatches by lymphocytotoxicity assay for all kidney transplants and for heart and lung transplants when the candidate has a positive panel reactive antibody (PRA) assay. A concept evolved that transplantations should not be performed across a positive cytotoxicity crossmatch. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients. This study plans to enroll 370 pediatric heart transplant recipients over a period of 3 years. The follow-up period will last up to 3 years. All participants will be enrolled pretransplant. In the pretransplant phase, visits will occur every 6 months. These routine visits will continue until transplant or the end of the study. They will coincide with routine pretransplant status visits. At the time of transplant, the participants will be assigned to one of two groups. Group A will include participants who are allo-antibody negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Cohort B will include participants who have the presence of a DTT-treated AHG CDC-PRA of greater than or equal to 10% and/or an ELISA-PRA greater than or equal to 10% in any pretransplant sample. Both cohorts will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, and, those in the sensitized group will have additional blood testing performed after the transplant and lasting until the end of the study. Post-transplant visits will occur while participants are recovering in the hospital; at Months 1, 3, and 6; and annually until the study closes. The information collected for the study include data from a physical exam, routine testing, adverse (AEs) and serious adverse (SAEs) events assessments, and blood collection. Each time a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If stored tissue is not available, none will be collected. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3O03JFGI6 | ||||||
| Subjects: | 290 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1618: Superior mouse eosinophil depletion in vivo targeting transgenic Siglec-8 instead of endogenous Siglec-F: mechanisms and pitfalls | |||||||
| Status: | New | ||||||
| Description: | We uncovered shortcomings when using certain antibodies that target Siglec-F to deplete mouse eosinophils, while administration of anti-Siglec-8 antibody to Siglec-8 transgenic mice works well. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M348T28T35 | ||||||
| Subjects: | 12 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1626: Transcriptome and Regulatory Maps of Decidua-derived Stromal Cells Inform Gene Discovery in Preterm Birth | |||||||
| Status: | New | ||||||
| Description: | While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWAS), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of comprehensive functional genomic annotations in human cell types relevant to pregnancy and PTB. Here, we generated extensive transcriptional and chromatin annotations of cultured primary decidua-derived mesenchymal stromal/stem cells (MSCs) and in vitro differentiated decidual stromal cells (DSCs) and developed a computational framework to integrate these functional annotations with results from a GWAS of gestational duration in 56,384 women. This resulted in a significant enrichment of heritability estimates in functional noncoding regions in stromal cells, as well as in the discovery of additional loci associated with gestational duration and target genes of associated loci. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3FQ76H3IG | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1627: Single-site, five-year experience with human eosinophil isolation by density gradient centrifugation and CD16 immunomagnetic negative separation | |||||||
| Status: | New | ||||||
| Description: | Little has been reported regarding the reliability of methods for the purification of human blood eosinophils. We retrospectively reviewed our experience with 350 consecutive eosinophil isolations. | ||||||
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| DOI: | 10.21430/M35EOMB2WH | ||||||
| Subjects: | 83 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1632: T cell and chemokine receptor control of CD8 T cell motility after influenza infection | |||||||
| Status: | New | ||||||
| Description: | In mice, experimental influenza virus infection stimulates CD8 T cell infiltration of the airways. Virus is cleared by day 9, and between days 8 and 9 there is an abrupt change in CD8 T cell motility behavior transitioning from low velocity and high confinement on day 8, to high velocity with continued high confinement on day 9. We hypothesized that loss of virus and/or antigen signals in the context of high chemokine levels drives the T cells into a rapid surveillance mode. Virus infection induces chemokine production, which may change when the virus is cleared. We therefore sought to examine this period of rapid changes to the T cell environment in the tissue and seek evidence on the roles of peptide-MHC and chemokine receptor interactions. Experiments were performed to block G protein coupled receptor (GPCR) signaling with Pertussis toxin (Ptx). Ptx treatment generally reduced cell velocities and mildly increased confinement suggesting chemokine mediated arrest (velocity <2 ?m/min) [1], except on day 8 when velocity increased and confinement was relieved. Blocking specific peptide-MHC with monoclonal antibody unexpectedly decreased velocities on days 7 through 9, suggesting TCR/peptide-MHC interactions promote cell mobility in the tissue. Together, these results suggest the T cells are engaged with antigen bearing and chemokine producing cells that affect motility in ways that vary with the day after infection. The increase in velocities on day 9 were reversed by addition of specific peptide, consistent with the idea that antigen signals become limiting on day 9 compared to earlier time points. Thus, antigen and chemokine signals act to alternately promote and restrict CD8 T cell motility until the point of virus clearance, suggesting the switch in motility behavior on day 9 may be due to a combination of limiting antigen in the presence of high chemokine signals as the virus is cleared. | ||||||
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| DOI: | 10.21430/M3H6B9CA5D | ||||||
| Subjects: | 27 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1636: Crowdsourcing Assessment of Maternal Blood Multi-omics for Predicting Gestational Age and Preterm Birth | |||||||
| Status: | New | ||||||
| Description: | Identification of pregnancies at risk of preterm birth (PTB), the leading cause of newborn deaths, remains challenging given the syndromic nature of the disease. We report a longitudinal multi-omics study coupled with a DREAM challenge to develop predictive models of PTB. We found that whole blood gene expression predicts ultrasound-based gestational ages in normal and complicated pregnancies, as well as the delivery date in normal pregnancies, with an accuracy similar to ultrasound. However, unlike the latter, transcriptomic data collected <37 weeks of gestation predicted the delivery date of one third of spontaneous (sPTB) cases within 2 weeks of the actual date. When only those samples collected <33 weeks from asymptomatic women were used, we found expression changes preceding preterm prelabor rupture of the membranes that were consistent across time points and cohorts, involving, among others, leukocyte-mediated immunity. Plasma proteomic data predicted sPTB with higher accuracy and earlier in pregnancy than whole blood transcriptomic data. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M31T6SHTYD | ||||||
| Subjects: | 0 | ||||||
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| Publications: | None | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1637: Immune phenotyping of diverse syngeneic murine brain tumors identifies immunologically distinct types (see companion study SDY1658) | |||||||
| Status: | New | ||||||
| Description: | Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. We generated distinct imageable syngeneic mouse GBM-tumor models and utilized RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells, resident macrophages and fewer eosinophils and SiglecF+ macrophages. To mimic the clinical settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decrease in resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM-tumors showed stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients. | ||||||
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| DOI: | 10.21430/M37FYK2I9O | ||||||
| Subjects: | 5 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1641: Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension | |||||||
| Status: | New | ||||||
| Description: | The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. | ||||||
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| DOI: | 10.21430/M3YGG9R72B | ||||||
| Subjects: | 42 | ||||||
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| SDY1642: Establishment of Vaginal Microbiota Composition in Early Pregnancy and its Association with Subsequent Preterm Prelabor Rupture of the Fetal Membrane | |||||||
| Status: | New | ||||||
| Description: | Vaginal bacterial community composition influences pregnancy outcome. Preterm prelabor rupture of the fetal membranes (PPROM), which precedes 30% of all spontaneous preterm births, is associated with high vaginal bacterial diversity prior to rupture. The point at which vaginal bacterial diversity is established before PPROM is unknown. In this study, we use metataxonomics to longitudinally characterize the vaginal bacterial composition from as early as 6 weeks of gestation in women at high (n = 38) and low (n = 22) risk of preterm birth who subsequently experience PPROM and in women delivering at term without complications (n = 36). Reduced Lactobacillus spp. abundance and high diversity was observed prior to PPROM in 20% and 26% of women at low and high risk of preterm births respectively, but in only 3% of women who delivered at term. PPROM was associated with instability of bacterial community structure during pregnancy and a shift toward higher diversity predominately occurring during the second trimester. This was characterized by increased relative abundance of potentially pathogenic species including Prevotella, Peptoniphilus, Streptococcus, and Dialister. This study identifies reduced Lactobacillus spp. abundance and increasing vaginal bacterial diversity as an early risk factor for PPROM and highlights the need for interventional studies designed to assess the impact of modifying vaginal bacterial composition for the prevention of preterm birth. | ||||||
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| DOI: | 10.21430/M3GL2SM9XS | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1649: Cervicovaginal Microbiota and Local Immune Response Modulate the Risk of Spontaneous Preterm Delivery | |||||||
| Status: | New | ||||||
| Description: | Failure to predict and understand the causes of preterm birth, the leading cause of neonatal morbidity and mortality, have limited effective interventions and therapeutics. From a cohort of 2000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Using innovative Bayesian modeling of cervicovaginal microbiota, seven bacterial taxa were significantly associated with increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of beta-defensin-2 lowered the risk of sPTB associated with cervicovaginal microbiota in an ethnicity-dependent manner. Surprisingly, even in Lactobacillus spp. dominated cervicovaginal microbiota, low beta-defensin-2 was associated with increased risk of sPTB. These findings hold promise for diagnostics to accurately identify women at risk for sPTB early in pregnancy. Therapeutic strategies could include immune modulators and microbiome-based therapeutics to reduce this significant health burden. | ||||||
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| DOI: | 10.21430/M3LUWFE0DS | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1656: Sublingual Cockroach Safety Study (SCSS) (ICAC-10) | |||||||
| Status: | New | ||||||
| Description: | Immunotherapy may help reduce symptoms of allergy and asthma. Problems concerning compliance and adverse events with subcutaneous allergen immunotherapy have generated interest in delivering immunotherapy sublingually (under the tongue). The purpose of this study is to evaluate the safety of a cockroach extract given sublingually to people with perennial (year-round) allergic rhinitis, with or without asthma. | ||||||
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| DOI: | 10.21430/M36VE0UMF1 | ||||||
| Subjects: | 28 | ||||||
| Study PI, contact: |
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1657: The Underlying Mechanisms For S. Aureus Infection And Colonization Of Skin in People With Atopic Dermatitis With And Without Eczema Herpeticum (MRSA) (ADVN-10) | |||||||
| Status: | New | ||||||
| Description: | The emergence of drug-resistant staphylococcal strains was first seen in the US almost a decade ago, when the Centers for Disease Control (CDC) reported four fatal community-based MRSA infections in children. In recent years, MRSA has grown into a serious public health concern with an increasing number of both hospital-acquired and community-acquired cases being seen. There will be approximately 130 participants recruited for this trial. The study population will consist of people with Atopic Dermatitis (AD) and people without Atopic Dermatitis (non-atopic). AD is a skin disorder with an itchy, red skin rash. People with AD are more likely to get bacterial and viral skin infections, possibly because they lack certain proteins in their skin, which help the body's immune system to fight infections. AD people with a history of Eczema Herpeticum (EH) may also be at greater risk for being infected with MRSA. This could be due to extended treatment courses with staphylococcal antibiotics, especially because overuse and misuse of antibiotics can lead to bacterial antibiotic resistance. The precise reasons are unknown. The purpose of this study is to determine the reasons for infection in AD participants with and without a history of EH. Investigators are seeking to recruit patients with either Methicillin-sensitive staphylococcus aureus (MSSA) or MRSA bacteria on their skin, so that they may adequately study potential factors related to MRSA infection. Investigators will determine if the MRSA collected from people with AD is primarily community or hospital associated. They will also determine if the proteins on the skin of ADEH+ people with MRSA differ from the proteins on the skin of AD people with MSSA or people without AD, or if there are any marked differences in serum total IgE levels between AD subjects with MRSA, MSSA, or without S. aureus. Approximately 60 ADEH+ and 60 ADEH- participants will need to be enrolled to find participants with MRSA or MSSA on their skin. Presence of these bacteria on the skin can only be determined once skin swabs are collected and tested. If participants are deemed eligible at screening, they will continue on to the study visit, which will last for approximately 2-3 hours. At the study visit, participants will be asked to provide information related to their medical history including infection, hospitalization, and medication record. Additionally, a skin exam will be performed to verify diagnosis (ADEH-, ADEH+, or non-atopic); nasal and skin swabs samples will be collected; tape strippings samples will be collected; and a blood sample will be collected. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M35H10G9TD | ||||||
| Subjects: | 65 | ||||||
| Study PI, contact: |
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1658: A comparative CyTOF analysis of resected-tumor samples from human GBM patients and mouse GBM-tumors (see companion study SDY1637) | |||||||
| Status: | New | ||||||
| Description: | Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. We generated distinct imageable syngeneic mouse GBM-tumor models and utilized RNA-sequencing, CyTOF and correlative immunohistochemistry to assess immune-profiles in these models. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous exhausted CD8 T cells, resident macrophages and fewer eosinophils and SiglecF+ macrophages. To mimic the clinical settings of first line of GBM-treatment, we show that tumor-resection invigorates an anti-tumor response via increasing T cells, activated microglia and SiglecF+ macrophages and decrease in resident macrophages. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM-tumors showed stark similarities in one of the mouse GBM-tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients. | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3QCK8H0YH | ||||||
| Subjects: | 16 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY520: Immunologic and genomic signatures of influenza vaccine response - 2013 (see companion studies SDY63, SDY404, SDY400) | |||||||
| Status: | Updated | ||||||
| Description: | Project 1: Immunologic and genomic signatures of influenza vaccine response - year4 2013 | ||||||
| Program/Contract: |
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| DOI: | 10.21430/M3KVVHM735 | ||||||
| Subjects: | 61 | ||||||
| Study PI, contact: |
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1468: B-cell Immunity to Influenza (SLVP017) 2010 | |||||||||
| Status: | Updated | ||||||||
| Description: | Systems biology approach to examine effects of seasonal flu vaccination in adults of different ages on gene expression, cytokine stimulation and serum cytokines with parameters such as immune senescence to uncover new markers and mechanisms behind failure of immune function in many older people. | ||||||||
| Program/Contract: |
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| DOI: | 10.21430/M30IB1ZZDJ | ||||||||
| Subjects: | 71 | ||||||||
| Study PI, contact: |
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| Clinical Assessments: | None | ||||||||