DR25 DataRelease
Release Date: 01/04/2018
| SDY1039: Scleroderma: Cyclophosphamide or Transplantation (SCOT) | |||||
| Status: | New | ||||
| Description: | This prospective, randomized, open-label, multi-center, 2-arm, Phase II clinical trial will randomize approximately 114 subjects with severe SSc in the United States and Canada. Subjects will be randomly assigned in a 1:1 ratio to a treatment of high-dose immunosuppressive therapy with autologous stem cell rescue (HDIT transplantation) or to treatment of monthly pulse IV cyclophosphamide. Subjects will be stratified by treatment center. The initial treatment period will be approximately 3 months for the HDIT transplantation arm (from the time of initiation of mobilization until the day of transplant) and 12 months for the cyclophosphamide arm. Subjects will be followed for up to 72 months after randomization. The study will continue for 54 months after the last subject is randomized. | ||||
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| DOI: | 10.21430/M3SM4YLTLH | ||||
| Subjects: | 75 | ||||
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| Assays: | None | ||||
| Clinical Assessments: | None | ||||
| SDY1045: KIR and HLA in MS | |||||||
| Status: | New | ||||||
| Description: | The association of specific alleles and haplotypes at the HLA class I and class II loci with a variety of autoimmune diseases is well established. Recently, polymorphisms in the Killer Immunoglobulin-like Receptors (KIR) genes that encode the stimulatory and inhibitory receptors on NK cells have been reported to be associated with a few of the same HLA-associated diseases, (e.g. psoriatic arthritis, scleroderma, and T1D). The ligands recognized by many of these receptors are epitopes on HLA class I molecules. In this study, we examine the role of HLA and KIR alleles, haplotypes, and KIR gene-HLA ligand pairs with a clinically well-defined Multiple Sclerosis cohort and ethnically matched controls using our Roche 454 GS FLX sequencing system for allelic resolution typing of HLA and our high-throughput MALDI-TOF KIR genotyping assay. | ||||||
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| DOI: | 10.21430/M3QW34U2SG | ||||||
| Subjects: | 831 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1171: Antibody-dependent enhancement of severe dengue disease in humans | |||||||
| Status: | New | ||||||
| Description: | For dengue viruses (DENV1-4), a specific range of antibody titer has been shown to enhance viral replication in vitro and severe disease in animal models. Although suspected, such antibody-dependent enhancement (ADE) of severe disease has not been shown to occur in humans. Using multiple statistical approaches to study a long-term pediatric cohort in Nicaragua, we show that risk of severe dengue disease is highest within a narrow range of pre-existing anti-DENV antibody titers. By contrast, we observe protection from all symptomatic dengue disease at high antibody titers. Thus, immune correlates of severe dengue must be evaluated separately from correlates of protection against symptomatic disease. These results have implications for studies of dengue pathogenesis and for vaccine development, because enhancement, not just lack of protection, is of concern.
Data are available upon request (eharris@berkeley.edu), as is required by the IRB-approved protocol for the Pediatric Dengue Cohort Study. The materials and data used in this study are covered by standard material transfer agreements. |
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| DOI: | 10.21430/M3NEL3QH3Q | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY1172: Systems Immunology of Malaria | ||||||||||||
| Status: | New | |||||||||||
| Description: | Immunity to malaria can be acquired through natural exposure to Plasmodium falciparum (Pf), but only after years of repeated infections. Typically, this immunity is acquired by adolescence and confers protection against disease, but Pf infection per se. Efforts to understand the mechanisms of this immunity are integral to the development of a vaccine that would mimic the induction of adult immunity in children. The current study applies systems biology approaches to a cohort from the rural village of Kalifabougou, Mali, where Pf transmission is intense and seasonal. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural Pf infection. The resulting datasets will be of considerable value in the urgent worldwide effort to develop a malaria vaccine that could prevent more than a million deaths annually. | |||||||||||
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| DOI: | 10.21430/M3CFFNO2V3 | |||||||||||
| Subjects: | 80 | |||||||||||
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| SDY1185: Dog Sarcoma Therapy | |||||||
| Status: | New | ||||||
| Description: | The drug eBAT is a bispecific angiotoxin targeted to both tumor and tumor neovasculature for sarcomas. It has been shown effectively kills canine hemangiosarcoma and human sarcoma cells in vitro. The paper studied the drug in an in vivo ?ontarget? companion dog trial. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I?II study of 23 dogs with spontaneous, stage I?II, splenic hemangiosarcoma. eBAT improved 6-month survival from <40% in a comparison population to approximately 70% in dogs treated at a biologically active dose (50 ?g/kg). Six dogs were long-term survivors, living >450 days. The expected targeted markers, uPAR and EGFR, are validated in both human and canine sarcoma samples. The results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies. | ||||||
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| DOI: | 10.21430/M3F266SILJ | ||||||
| Subjects: | 114 | ||||||
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| Clinical Assessments: | None | ||||||
| SDY1205: PTB-associated ancestry variants identification through genome-wide analysis | ||||||||||
| Status: | New | |||||||||
| Description: | Preterm birth (PTB), the delivery of an infant prior to 37 weeks of gestation, is a significant determinant of infant morbidity and mortality. The vast majority of PTBs are spontaneous, caused by either preterm labor or preterm premature rupture of membranes (PPROM). The exact mechanism of spontaneous PTB is unknown, though a multitude of social, environmental, and maternal factors have been implicated. Various observations, such as the tendency for recurrent PTBs and the increased risk of preterm delivery for women who themselves were born preterm, suggest a heritable component to the risk of PTB. Twin studies estimate that maternal genetic variants account for approximately 27% to 36% of the incidence of PTB. A recent study estimated that 11% of variation is due to fetal genetic effects, and a follow up study found a significant effect in individuals with European ancestry, but not African Americans. PTB rates vary among races and ethnicities, with significantly higher rates observed in African Americans, though it is currently unclear how the genetics of PTB differ across groups. This study is a cross-ethnic, ancestry-informed GWAS analysis of 1,349 infants born prematurely. A large cohort of over 12,000 individuals obtained by leveraging publicly available data served as a control cohort. Using this approach, after extensive filtering and quality control, two intergenic variants, statistically significantly associated with PTB were identified. Several existing replication cohorts were queried and no support of these associations were found. The authors concludes that the fetal genetic contribution to PTB is unlikely due to single common genetic variant, but could be explained by interactions of multiple common variants, or of rare variants affected by environmental influences, all not detectable using a GWAS alone. | |||||||||
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| DOI: | 10.21430/M37N6PJEQT | |||||||||
| Subjects: | 0 | |||||||||
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| Assays: | None | |||||||||
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| SDY1206: Early pregnancy vaginal microbiome trends and preterm birth (see companion study SDY1341) | ||||||||||
| Status: | New | |||||||||
| Description: | Previous studies have shown that vaginal microbiota of asymptomatic, nonpregnant, reproductive age women cluster into 5 distinct ?community-state types?, which differ both by dominant Lactobacillus species as well as overall community composition. A much greater proportion of African-American and Hispanic women harbored a non-Lactobacillus-dominant community, suggesting that in some women a non-Lactobacillus-based vaginal community may be a normal variant. A recent study examined vaginal microbial composition and the risk for preterm birth but had very few African-American subjects and few preterm births. This study characterizes vaginal microbial community characteristics over time in a large predominantly African-American cohort of pregnant women and test whether particular community characteristics are associated with the risk for subsequent preterm birth. | |||||||||
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| DOI: | 10.21430/M3H1U3KJMZ | |||||||||
| Subjects: | 77 | |||||||||
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| SDY1215: Mitochondrial and Nuclear Ancestry Association to PTB | |||||||
| Status: | New | ||||||
| Description: | The risk of preterm birth is unequally distributed between different ethnic groups. African American women are at increased risk for delivering preterm compared with the population as a whole. Determining the etiologies responsible for this heightened risk is complex, because it can be difficult to distinguish environmental and genetic influences. Attempts to elucidate such influences have evaluated carefully controlled populations, such as members of the military, to conclude that African ancestry is an independent risk factor. Specifying genetic risk factors in a related group is greatly complicated by false attribution, but a possible link between Americans of African descent is that African haplogroup mitochondrial DNA (mtDNA) is highly prevalent in this group. Matrilineal pedigree and mitochondrial ancestry are both consistent with a mitochondria-inherited risk factor. There is also evidence that mitochondrial function is important for the maintenance of pregnancy. However, attempts to link preterm birth to specific polymorphisms in mtDNA in case-control studies failed to identify polymorphisms associated with preterm birth. Thus, it remains unclear how a mtDNA-specific inheritance pattern could be associated with a common outcome like preterm birth. Mitochondrial haplogroup and nuclear ancestry for individuals were determined and used to develop a scoring for the degree to which mitochondrial ancestry is divergent from nuclear ancestry. Infants with higher degrees of divergent mitochondrial ancestry were at increased risk for preterm birth (0.124 for preterm vs 0.105 for term infants; P < .05). This finding was validated in 1 of 2 replication cohorts. Greater degrees of divergent ancestry correlating with earlier delivery within the primary study population was observed, but this finding was not replicated in secondary cohorts born preterm. Individuals with divergent patterns of mitochondrial and nuclear ancestry are at increased risk for preterm birth. These findings may in part explain the higher rates of preterm birth in African Americans and in individuals with a matrilineal family history of preterm birth. | ||||||
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| DOI: | 10.21430/M3VCNPMD4B | ||||||
| Subjects: | 0 | ||||||
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| Assays: | None | ||||||
| Clinical Assessments: | None | ||||||
| SDY997: AMP Lupus Network Project: Molecular Characterization of Lupus Nephritis and Correlation with Response to Therapy | ||||||||||
| Status: | Updated | |||||||||
| Description: | Phase I will be devoted to the study of at least 45 subjects with lupus nephritis and 25 controls with the intent of achieving the following goals: (i) to assess feasibility of obtaining a sufficient yield of high quality data based on current and refined AMP SOPs, (ii) to assess recruitment rates and the number of sites necessary to effectively recruit for Phase II, (iii) to ensure that the technologies developed in Phase 0 are working well, especially with regard to transport and scaling up to handle specimens from multiple sites; (iv) to demonstrate that the selected technologies can be used for the purpose of reliably differentiating lupus nephritis kidneys from kidney tissue without lupus nephritis, (v) where necessary, to further refine the technologies before embarking on a large-scale project; and most importantly (vi) to provide critical data upon which to make rational decisions about key elements of the Phase II study design (e.g., eligibility criteria, estimates of variation for power calculations, and site-specific capability regarding patient recruitment, specimen handling, etc.). | |||||||||
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| DOI: | 10.21430/M35FLWNXH1 | |||||||||
| Subjects: | 105 | |||||||||
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| Publications: | None | |||||||||
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| SDY998: AMP Rheumatoid Arthritis Arthroplasty Phase 1 | ||||||||||||||||||||||||||||
| Status: | Updated | |||||||||||||||||||||||||||
| Description: | The primary goal for RA arthroplasty P1 studies are: To establish if molecular signatures and pathways identified using core AMP technologies differ between OA and RA in 20 RA surgical samples and 10 OA arthroplasty samples. | |||||||||||||||||||||||||||
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| DOI: | 10.21430/M3KXJHSP4T | |||||||||||||||||||||||||||
| Subjects: | 40 | |||||||||||||||||||||||||||
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| Publications: | None | |||||||||||||||||||||||||||
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| SDY999: AMP Rheumatoid Arthritis Synovial Phase 1 | |||||||||||||||||||||||||
| Status: | Updated | ||||||||||||||||||||||||
| Description: | The primary goal for RA synovial P1 studies are: To establish feasibility of obtaining ultrasound-guided synovial biopsies in the United States (U.S.) by comparing to frozen synovial biopsies obtained in the United Kingdom (U.K.) | ||||||||||||||||||||||||
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| DOI: | 10.21430/M3XRJHRPBC | ||||||||||||||||||||||||
| Subjects: | 22 | ||||||||||||||||||||||||
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| Publications: | None | ||||||||||||||||||||||||
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| SDY1164: Vaginal microbial signature for preterm birth | |||||||
| Status: | Updated | ||||||
| Description: | Recent studies about association between maternal vaginal microbiota and risks for preterm birth (PTB) conflicted along similar lines: Caucasian and Asian women cohorts showed associations between PTB and low Lactobacillus vaginal communities (BV-like) while no significant association with PTB was detected in cohorts of African-American women. This study compares two new larger cohorts of women at low and high risk for PTB, addressing two challenges: (i) low power resulting from the combination of small study populations (30?91 pregnant women), the many taxa measured by metabarcoding, and the absence of initial hypotheses more specific than some difference between preterm and term gestations; and (ii) insufficient understanding of population-specific factors that might modulate the PTB?microbiota association. | ||||||
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| DOI: | 10.21430/M37W3869AH | ||||||
| Subjects: | 136 | ||||||
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| SDY1176: Extensive homeostatic T cell phenotypic variation within the Collaborative Cross | |||||||
| Status: | Updated | ||||||
| Description: | The Collaborative Cross (CC) is a panel of reproducible recombinant inbred mouse strains with high levels of standing genetic variation, thereby affording unprecedented opportunity to perform experiments in a small animal model containing controlled genetic diversity while allowing for genetic replicates. Here, we advance the utility of this unique mouse resource for immunology research, as it allows for both examination and genetic dissection of mechanisms behind adaptive immune states in mice with distinct and defined genetic makeups. This approach is founded on quantitative trait locus mapping: identifying genetically variant genome regions associated with phenotypic variance in traits-of-interest. Furthermore, the CC can be utilized for mouse model development; distinct strains have unique immunophenotypes and immune properties, making them suitable for research on particular diseases and infections. Here, we describe variation in cellular immune phenotypes across F1 crosses of CC strains, and reveal novel quantitative trait loci responsible for several immune phenotypes. | ||||||
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| DOI: | 10.21430/M3RKBKOYKS | ||||||
| Subjects: | 476 | ||||||
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| Publications: | None | ||||||
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| Clinical Assessments: | None | ||||||