10,659 results match your criteria stanford immunology

Actionable druggable genome-wide Mendelian randomization identifies repurposing opportunities for COVID-19.

Nat Med 2021 Apr 9. Epub 2021 Apr 9.

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA.

Drug repurposing provides a rapid approach to meet the urgent need for therapeutics to address COVID-19. To identify therapeutic targets relevant to COVID-19, we conducted Mendelian randomization analyses, deriving genetic instruments based on transcriptomic and proteomic data for 1,263 actionable proteins that are targeted by approved drugs or in clinical phase of drug development. Using summary statistics from the Host Genetics Initiative and the Million Veteran Program, we studied 7,554 patients hospitalized with COVID-19 and >1 million controls. Read More

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Distinct clinical phenotypes for Crohn's disease derived from patient surveys.

BMC Gastroenterol 2021 Apr 9;21(1):160. Epub 2021 Apr 9.

Department of Bioengineering, Stanford University, Shriram Room 209, MC: 4245, 443 Via Ortega Drive, Stanford, CA, 94305-4145, USA.

Background: Defining clinical phenotypes provides opportunities for new diagnostics and may provide insights into early intervention and disease prevention. There is increasing evidence that patient-derived health data may contain information that complements traditional methods of clinical phenotyping. The utility of these data for defining meaningful phenotypic groups is of great interest because social media and online resources make it possible to query large cohorts of patients with health conditions. Read More

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Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network.

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224;

Intracellular protein homeostasis is maintained by a network of chaperones that function to fold proteins into their native conformation. The eukaryotic TRiC chaperonin (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1) facilitates folding of a subset of proteins with folding constraints such as complex topologies. To better understand the mechanism of TRiC folding, we investigated the biogenesis of an obligate TRiC substrate, the reovirus σ3 capsid protein. Read More

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COVID-19 vaccination in mastocytosis: recommendations of the European Competence Network on Mastocytosis (ECNM) and American Initiative in Mast Cell Diseases (AIM).

J Allergy Clin Immunol Pract 2021 Apr 5. Epub 2021 Apr 5.

Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Covid-19 is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Read More

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Genome-wide enhancer maps link risk variants to disease genes.

Nature 2021 Apr 7. Epub 2021 Apr 7.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Genome-wide association studies (GWAS) have identified thousands of noncoding loci that are associated with human diseases and complex traits, each of which could reveal insights into the mechanisms of disease. Many of the underlying causal variants may affect enhancers, but we lack accurate maps of enhancers and their target genes to interpret such variants. We recently developed the activity-by-contact (ABC) model to predict which enhancers regulate which genes and validated the model using CRISPR perturbations in several cell types. Read More

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Emerging concepts in the science of vaccine adjuvants.

Nat Rev Drug Discov 2021 Apr 6. Epub 2021 Apr 6.

GSK Vaccines, Rockville, MD, USA.

Adjuvants are vaccine components that enhance the magnitude, breadth and durability of the immune response. Following its introduction in the 1920s, alum remained the only adjuvant licensed for human use for the next 70 years. Since the 1990s, a further five adjuvants have been included in licensed vaccines, but the molecular mechanisms by which these adjuvants work remain only partially understood. Read More

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Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.

NPJ Biofilms Microbiomes 2021 04 6;7(1):31. Epub 2021 Apr 6.

Department of Otolaryngology, Head and Neck Surgery, Stanford University, Stanford, CA, USA.

Chronic suppurative otitis media (CSOM) is a widespread, debilitating problem with poorly understood immunology. Here, we assess the host response to middle ear infection over the course of a month post-infection in a mouse model of CSOM and in human subjects with the disease. Using multiparameter flow cytometry and a binomial generalized linear machine learning model, we identified Ly6G, a surface marker of mature neutrophils, as the most informative factor of host response driving disease in the CSOM mouse model. Read More

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North American musculoskeletal ultrasound scanning protocol of the hip, knee, ankle, and foot: update of a Delphi consensus study.

Clin Rheumatol 2021 Apr 5. Epub 2021 Apr 5.

John Muir Hospital, Walnut Creek, CA, USA.

Background/objective: A North American rheumatology consensus on tiered-mastery designation for anatomic views was developed in 2011 for course and fellowship teaching. This study updates the lower extremity joint scanning protocols aiming to inform musculoskeletal ultrasound curriculum development for the American College of Rheumatology affiliated Fellowship Programs.

Methods: Three Delphi rounds were conducted to reach consensus for tiered-level mastery designation for hip, knee, ankle, and foot scanning views. Read More

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Interrogating immune cells and cancer with CRISPR-Cas9.

Trends Immunol 2021 Mar 31. Epub 2021 Mar 31.

Program in Immunology, Stanford University School of Medicine, Stanford, CA, USA; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA. Electronic address:

CRISPR-Cas9 technologies have transformed the study of genetic pathways governing cellular differentiation and function. Recent advances have adapted these methods to immune cells, which has accelerated the pace of functional genomics in immunology and enabled new avenues for the design of cellular immunotherapies for cancer. In this review, we summarize recent developments in CRISPR-Cas9 technology and discuss how they have been leveraged to discover and manipulate novel genetic regulators of the immune system. Read More

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Vaccines and Allergic reactions: the past, the current COVID-19 pandemic, and future perspectives.

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, CA, USA.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. Read More

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Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94304;

Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells. Read More

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HIV-1 Subtype C Drug Resistance Mutations in Heavily Treated Patients Failing Integrase Strand Transfer Inhibitor-Based Regimens in Botswana.

Viruses 2021 Mar 31;13(4). Epub 2021 Mar 31.

Botswana Harvard AIDS Institute Partnership, Gaborone 0000, Botswana.

There are limited real-world mutational and virological outcomes data of treatment-experienced persons diagnosed with HIV-1 subtype C (HIV-1 C) who are failing Integrase Strand Transfer Inhibitor-based regimens. Requisition forms sent for HIV-1 genotypic resistance testing (GRT) between May 2015 and September 2019 were reviewed and participants experiencing virologic failure while on dolutegravir (DTG) or raltegravir (RAL) cART at sampling recruited. Sanger sequencing of the HIV-1 Pol gene was performed from residual plasma samples and drug resistance mutational (DRM) analysis performed using the Stanford University HIV drug resistance database. Read More

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Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids.

Pharmaceuticals (Basel) 2021 Mar 31;14(4). Epub 2021 Mar 31.

Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.

Viral infections, such as those caused by Herpes Simplex Virus-1 (HSV-1) and SARS-CoV-2, affect millions of people each year. However, there are few antiviral drugs that can effectively treat these infections. The standard approach in the development of antiviral drugs involves the identification of a unique viral target, followed by the design of an agent that addresses that target. Read More

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Carbon Nanotubes-Potent Carriers for Targeted Drug Delivery in Rheumatoid Arthritis.

Pharmaceutics 2021 Mar 27;13(4). Epub 2021 Mar 27.

Department of Chemistry, Technical University of Denmark, Kemitorvet 206, 2800 Kongens Lyngby, Denmark.

Two types of single-walled carbon nanotubes (SWCNTs), HiPco- and carboxyl-SWCNT, are evaluated as drug carriers for the traditional anti-inflammatory drug methotrexate (MTX) and a small interfering RNA (siRNA) targeting NOTCH1 gene. The nanotubes are solubilized by PEGylation and covalently loaded with MTX. The coupling efficiency (CE%) of MTX is 77-79% for HiPco-SWCNT and 71-83% for carboxyl-SWCNT. Read More

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Trends in emergency department visits and hospitalizations for acute allergic reactions and anaphylaxis among US older adults: 2006-2014.

J Allergy Clin Immunol Pract 2021 Mar 30. Epub 2021 Mar 30.

Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Department of Emergency Medicine, Massachusetts General Hospital, Boston, MA.

Background: The US older adult population (≥65 years) is increasing and may be at increased risk for severe anaphylaxis. Little is known about the healthcare utilization for acute allergic reactions (AAR), including anaphylaxis, among older adults.

Objectives: To characterize trends in emergency department (ED) visits and hospitalizations for AAR and anaphylaxis among US older adults from 2006-2014, and to examine factors associated with severe anaphylaxis. Read More

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Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling.

Science 2021 04;372(6537)

Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

T cell exhaustion limits immune responses against cancer and is a major cause of resistance to chimeric antigen receptor (CAR)-T cell therapeutics. Using murine xenograft models and an in vitro model wherein tonic CAR signaling induces hallmark features of exhaustion, we tested the effect of transient cessation of receptor signaling, or rest, on the development and maintenance of exhaustion. Induction of rest through enforced down-regulation of the CAR protein using a drug-regulatable system or treatment with the multikinase inhibitor dasatinib resulted in the acquisition of a memory-like phenotype, global transcriptional and epigenetic reprogramming, and restored antitumor functionality in exhausted CAR-T cells. Read More

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The transcriptional landscape of Venezuelan equine encephalitis virus (TC-83) infection.

PLoS Negl Trop Dis 2021 Mar 31;15(3):e0009306. Epub 2021 Mar 31.

Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.

Venezuelan Equine Encephalitis Virus (VEEV) is a major biothreat agent that naturally causes outbreaks in humans and horses particularly in tropical areas of the western hemisphere, for which no antiviral therapy is currently available. The host response to VEEV and the cellular factors this alphavirus hijacks to support its effective replication or evade cellular immune responses are largely uncharacterized. We have previously demonstrated tremendous cell-to-cell heterogeneity in viral RNA (vRNA) and cellular transcript levels during flaviviral infection using a novel virus-inclusive single-cell RNA-Seq approach. Read More

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Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial.

Nat Commun 2021 03 30;12(1):1967. Epub 2021 Mar 30.

Department of Medicine, Stanford University, Stanford, CA, USA.

Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0. Read More

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Precise regulation of the relative rates of surface area and volume synthesis in bacterial cells growing in dynamic environments.

Nat Commun 2021 03 30;12(1):1975. Epub 2021 Mar 30.

Department of Bioengineering, Stanford University, Stanford, CA, USA.

The steady-state size of bacterial cells correlates with nutrient-determined growth rate. Here, we explore how rod-shaped bacterial cells regulate their morphology during rapid environmental changes. We quantify cellular dimensions throughout passage cycles of stationary-phase cells diluted into fresh medium and grown back to saturation. Read More

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Immune Changes Beyond Th2 Pathways During Rapid Multifood Immunotherapy enabled with Omalizumab.

Allergy 2021 Mar 30. Epub 2021 Mar 30.

Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USA.

Background: Multifood Oral Immunotherapy (mOIT) with adjunctive anti-IgE (omalizumab, Xolair ) treatment affords safe, effective, and rapid desensitization to multiple foods, although the specific immune mechanisms mediating this desensitization remain to be fully elucidated.

Methods: Participants in our phase 2 mOIT trial (NCT02643862) received omalizumab from baseline to week 16 and mOIT from week 8 to week 36. We compared the immune profile of PBMCs and plasma taken at baseline, week 8 and week 36 using high-dimensional mass cytometry, component-resolved diagnostics, the indirect basophil activation test, and Luminex. Read More

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Potent neutralization of Rift Valley fever virus by human monoclonal antibodies through fusion inhibition.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232;

Rift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here, we report the isolation of a panel of monoclonal antibodies (mAbs) from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins. Read More

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Chlorhexidine Gluconate Bathing Reduces the Incidence of Bloodstream Infections in Adults Undergoing Inpatient Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 Mar 7;27(3):262.e1-262.e11. Epub 2021 Jan 7.

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, North Carolina. Electronic address:

Bloodstream infections (BSIs) occur in 20% to 45% of inpatient autologous and allogeneic hematopoietic cell transplant (HCT) patients. Daily bathing with the antiseptic chlorhexidine gluconate (CHG) has been shown to reduce the incidence of BSIs in critically ill patients, although very few studies include HCT patients or have evaluated the impact of compliance on effectiveness. We conducted a prospective cohort study with historical controls to assess the impact of CHG bathing on the rate of BSIs and gut microbiota composition among adults undergoing inpatient HCT at the Duke University Medical Center. Read More

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Comprehensive identification of somatic nucleotide variants in human brain tissue.

Genome Biol 2021 Mar 29;22(1):92. Epub 2021 Mar 29.

Department of Health Sciences Research, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, 55905, USA.

Background: Post-zygotic mutations incurred during DNA replication, DNA repair, and other cellular processes lead to somatic mosaicism. Somatic mosaicism is an established cause of various diseases, including cancers. However, detecting mosaic variants in DNA from non-cancerous somatic tissues poses significant challenges, particularly if the variants only are present in a small fraction of cells. Read More

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Smoking, Radiation Therapy, and Contralateral Breast Cancer Risk in Young Women.

J Natl Cancer Inst 2021 Mar 29. Epub 2021 Mar 29.

Memorial Sloan Kettering Cancer Center, New York, NY.

Evidence is mounting that cigarette smoking contributes to second primary contralateral breast cancer (CBC) risk. Whether radiation therapy (RT) interacts with smoking to modify this risk is unknown. In this multicenter, individually-matched case-control study, we examined the association between RT, smoking, and CBC risk. Read More

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B Cell Response to Vaccination.

Wei Luo Qian Yin

Immunol Invest 2021 Mar 27:1-22. Epub 2021 Mar 27.

Institute for Immunity, Transplantation & Infection, Stanford University School of Medicine, Stanford, California, USA.

As one of the most important weapons against infectious diseases, vaccines have saved countless lives since their first use in the late eighteenth century. Antibodies produced by effector B cells upon vaccination play a critical role in mediating protection. The past several decades of research have led to a revolution in our understanding of B cell response to vaccination. Read More

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The oncogene AAMDC links PI3K-AKT-mTOR signaling with metabolic reprograming in estrogen receptor-positive breast cancer.

Nat Commun 2021 03 26;12(1):1920. Epub 2021 Mar 26.

Cancer Epigenetics Group, The Harry Perkins Institute of Medical Research, The University of Western Australia, Perth, WA, Australia.

Adipogenesis associated Mth938 domain containing (AAMDC) represents an uncharacterized oncogene amplified in aggressive estrogen receptor-positive breast cancers. We uncover that AAMDC regulates the expression of several metabolic enzymes involved in the one-carbon folate and methionine cycles, and lipid metabolism. We show that AAMDC controls PI3K-AKT-mTOR signaling, regulating the translation of ATF4 and MYC and modulating the transcriptional activity of AAMDC-dependent promoters. Read More

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Interferon-α augments clinical efficacy of regulatory T cell depletion with denileukin diftitox in ovarian cancer.

Clin Cancer Res 2021 Mar 26. Epub 2021 Mar 26.

Department of Medicine, University of Texas Health San Antonio

Purpose: Immunotherapy treats some cancers, but not ovarian cancer (OC). Regulatory T cells (Tregs) impede anti-OC immunity but effective human Treg-directed treatments are lacking. We tested Treg depletion with denileukin diftitox (DD) {plus minus} interferon-α as OC immunotherapy. Read More

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Extracellular cGAMP is a cancer cell-produced immunotransmitter involved in radiation-induced anti-cancer immunity.

Nat Cancer 2020 Feb 24;1(2):184-196. Epub 2020 Feb 24.

Stanford ChEM-H, Stanford University, California, USA.

2'3'-cyclic GMP-AMP (cGAMP) is an intracellular second messenger that is synthesized in response to cytosolic double-stranded DNA and activates the innate immune STING pathway. Our previous discovery of its extracellular hydrolase ENPP1 hinted at the existence of extracellular cGAMP. Here, we detected that cGAMP is continuously exported but then efficiently cleared by ENPP1, explaining why it has previously escaped detection. Read More

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February 2020

Consensus on DEfinition of Food Allergy SEverity (DEFASE) an integrated mixed methods systematic review.

World Allergy Organ J 2021 Mar 11;14(3):100503. Epub 2021 Mar 11.

Allergy Unit - Area of Translational Research in Pediatric Specialities, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Background And Aims: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders. Read More

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