Immune System Diseases Commons^™

Targeting Natural Killer Cells For Improved Immunity And Control Of The Adaptive Immune Response., Stephen Pierce, Eric S. Geanes, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Natural killer (NK) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the innate immune system. Recently, NK cells have also emerged as key regulators of adaptive immunity and have become a prominent therapeutic target for cancer immunotherapy and infection control. NK cells display a diverse array of phenotypes and function. Determining how NK cells develop and are regulated is critical for understanding their role in both innate and adaptive immunity. In this review we discuss current research approaches into NK cell adaptive immunity and how these cells are being harnessed for improving …

Heterogeneous Nuclear Ribonucleoprotein K (Hnrnp K) Overexpression And Its Interaction With Runx1 Rna In Acute Myeloid Leukemia, Marisa Aitken

Dissertations and Theses (Open Access)

Acute myeloid leukemia (AML) is an often devastating hematologic malignancy with 5-year overall survival lingering near 20%. Acquiring a deeper understanding of molecular underpinnings of leukemogenesis will provide a basis for developing more effective therapeutic strategies for patients with AML.

Here, we identified overexpression of hnRNP K as a recurrent abnormality in a subset (~20%) of AML patients. High levels of this RNA-binding protein associated with inferior clinical outcomes in de novo AML. Thus, to evaluate its putative oncogenic capacity in myeloid disease, we overexpressed hnRNP K in murine hematopoietic stem and progenitor cells isolated from fetal liver cells (FLCs). …

Unique Case Of Anca-Negative Pauci-Immune Necrotizing Glomerulonephritis With Diffuse Alveolar Hemorrhage, Potentially Associated With Midostaurin, Jonathan D Pankow, Guillaume Richard-Carpentier, Naval G Daver, William F Glass, Jaya Kala

Faculty, Staff and Student Publications

We present a 61-year-old male with FLT3-mutated acute myeloid leukemia treated with midostaurin who developed acute kidney injury requiring hemodialysis and pulmonary renal syndrome. Antibodies to proteinase-3, myeloperoxidase, and glomerular basement membrane were negative. Renal biopsy confirmed acute pauci-immune focal necrotizing glomerulonephritis (GN) with fibrin crescents indicating rapidly progressing glomerulonephritis. He improved with pulse methylprednisolone, intravenous cyclophosphamide, and plasma exchange with resolution of hemoptysis. This case highlights the importance of prompt renal biopsy to guide early initiation of life-saving therapies. To our knowledge, this is the first reported case of ANCA-negative pauci-immune necrotizing GN likely secondary to midostaurin.

The Role Of Nutrition In Promoting Gut Health And Treating Chronic Illness Through The Attenuation Of Inflammation, Allison Dalton

HCA Healthcare Journal of Medicine

Over the millennia, the human body and microorganisms such as bacteria, viruses, archaea, protozoa and parasites have coevolved together forming an intimate relationship. These microorganisms are found on the skin, in the mouth, genitourinary tract and most abundantly in the large intestine of the digestive tract. States of microbial dysbiosis contribute to chronic inflammation, which can lead to the pathogenesis and progression of numerous diseases. Micro- and macro-nutrients as well as dietary patterns like the Mediterranean diet can help improve health outcomes.

Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

Post-Surgical Pyoderma Gangrenosum After Breast Surgery: A Case Series, Jahan Tajran, Daniella Anderson, Arif Chaudhry, Dennis Hammond

Medical Student Research Symposium

Background:

Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that is thought to be due to innate immune system dysfunction, specifically of neutrophils. PG has been well documented in patients with autoimmune disorders like Ulcerative Colitis and Rheumatoid Arthritis. PG can also present in surgical patients, imitating a potential wound infection and necrotizing fasciitis. Although PG is a diagnosis of exclusion, prompt recognition is essential to attaining desired aesthetic outcomes, especially with breast involvement. We present a case series of four patients who developed PG following breast surgery. We analyze each patient’s medical history, symptoms, wound progression and management …

The Great Imitator Strikes Again: A Case Of A Lupus Flare-Up Presenting Like An Acute Abdomen, Emmanouil Kiriakopoulos, Vanessa Perez, Robyn Hoelle

HCA Healthcare Journal of Medicine

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting all age groups and can manifest in various forms, often making the initial or successive presentations difficult to diagnose. Peritonitis secondary to lupus is a rare manifestation of this disease and the prevalence is said to be much lower in children. We present a case report of an adolescent male with a known history of lupus who presented to the emergency department with a clinical picture consistent with an acute surgical abdomen and underwent an appendectomy. Subsequent workup identified the culprit as a lupus-related peritonitis requiring corticosteroids for resolution.

Evidence To Support Hiv Prevention For Adolescent Girls And Young Women (Agyw) And Their Male Partners: Results From Malawi Dreams Studies With Agyw, Male Partners Of Agyw, Men Living With Hiv, And Program Implementing Partners, Nanlesta Pilgrim, Victor Mwapasa, Effie Chipeta, Wanangwa Chimwaza Manda, Nrupa Jani, Tracy Mcclair, Lyson Tenthani, Sanyukta Mathur

HIV and AIDS

Project SOAR, led by the Population Council, in partnership with the Center of Reproductive Health at the University of Malawi College of Medicine, conducted a research portfolio to generate evidence to reduce HIV risk among adolescent girls and young women (AGYW) and their male partners. The objectives of this implementation research were to generate evidence for describing HIV-related risk factors among AGYW; assess the extent to which the overall DREAMS project contributed toward the goal of reducing HIV risk among AGYW; and understand the characteristics of male partners and how to link them to HIV services, as well as retain …

Community-Based Hiv Treatment Service Delivery Model For Female Sex Workers In Tanzania: Evaluation Findings, Lung Vu, Waimar Tun, Louis Apicella, Jeremiah Kidola, Caterina Casalini, Gasper Mbita, Neema Makyao, Todd Koppenhaver, Erick Mlanga

HIV and AIDS

Project SOAR in collaboration with the National AIDS Control Program of the Government of Tanzania, National Institute of Medical Research, and Jhpiego’s Sauti Program, conducted an implementation science study to investigate the delivery of community-based antiretroviral treatment (ART) services to female sex workers (FSWs) in Tanzania. Studies from sub-Saharan Africa have shown improved HIV treatment outcomes, such as uptake of HIV services, retention in care, and increased dignity and quality of life, by using community-based delivery of HIV services. As detailed in this Project SOAR final report, the study assessed the effectiveness of the community-based ART delivery intervention in improving …

Strengthening Capacity For Assessment Of Hiv-Related Data Needs Among Key Populations To Inform Evidence-Based Responses, Amrita Rao, Nikita Viswasam, Stefan Baral

HIV and AIDS

Defining the HIV prevention and treatment needs of key populations who have disproportionate HIV acquisition and transmission risks has been particularly difficult in the context of generalized HIV epidemics where less attention has historically been placed on the HIV prevention and treatment needs of these groups. There is a gap in our understanding of the specific needs of—and ultimately the investment case for the added value of supporting—disproportionately burdened key populations in these settings. In response to this gap, Johns Hopkins University under the United States Agency for International Development (USAID)-funded Project SOAR implemented a project in partnership with collaborators, …

Adjuvant Therapy In Adrenocortical Carcinoma: Reflections And Future Directions, Sara Bedrose, Marilyne Daher, Lina Altameemi, Mouhammed Amir Habra

Faculty, Staff and Students Publications

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with high risk of recurrence despite macroscopically complete surgical resection. The main predictors of ACC recurrence include advanced disease stage, incomplete surgical resection, cortisol production, certain genetic alterations, and high proliferation rate (Ki-67 proliferation index). Mitotane has been the mainstay adjuvant therapy of ACC. However, the use of mitotane is based on retrospective and occasionally conflicting evidence. As mitotane levels can take a few months before reaching therapeutic levels, there is an emerging practice of combining platinum-based chemotherapy with mitotane in the adjuvant setting. Retrospective data indicate that radiotherapy is an …

The Interplay Of The Oral-Gut Microbiome With Chronic Inflammation In Rheumatoid Arthritis And Crohn's Disease, Anuradha Rampersaud

Mako: NSU Undergraduate Student Journal

Abstract

Rheumatoid Arthritis (RA) and Crohn’s Disease (CD) are both chronic inflammatory diseases that share developmental and treatment similarities. RA’s symptoms include swelling, stiffness, and pain in synovial joints, corresponding with bone and cartilage destruction. CD’s symptoms include abdominal pain, bowel obstruction, bloating, diarrhea, and fever. The purpose of this literature review was to investigate the links between these two diseases and propose future treatment and prevention targets. Current treatment for RA and CD aims to suppress inflammation by targeting its mediators. However, this review noted that there should be greater focus on resolving inflammation. Both diseases are characterized by …

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

The Elevated Systemic Cytokine Levels In Hiv Patients Are Not Associated With An Elevated Pulmonary Cytokine Environment., Rafael Fernandez-Botran, Andrea Reyes-Vega, Yasmany García, Chanakya Charan Tirumala, Praneet Kumar Srisailam, Anupama Raghuram, Paula Peyrani, Stephen P. Furmanek, Mahder A. Tella, Jeffrey D. Ritzenthaler, Jesse Roman, Julio A. Ramirez

Faculty and Staff Scholarship

Background

HIV-positive patients on anti-retroviral therapy (ART) are at higher risk of developing many non-AIDS related chronic diseases, including chronic obstructive pulmonary disease (COPD), compared to HIV-negative individuals. While the mechanisms are not clear, a persistent pro-inflammatory state appears to be a key contributing factor. The aims of this study were to investigate whether HIV-positive patients without COPD present evidence of potentially predisposing abnormal pulmonary cytokine/chemokine environment and to explore the relationship between pulmonary and systemic cytokine levels.

Methods

This study included 39 HIV-seropositive and 34 HIV-seronegative subjects without COPD. All were subjected to outpatient bronchoscopy with bronchoalveolar lavage fluid …

Synthesis And Preliminary Ex Vivo Testing Of Sirna Targeting Tcrb: A Proposed Therapy For The Treatment Of Autoimmunity, Nicholas J. Magazine

LSU Doctoral Dissertations

Abstract

Background:

As of 2018, the United States National Institutes of Health estimate that over half a billion people worldwide are affected by autoimmune disorders. Though these conditions are prevalent, treatment options remain relatively poor, relying primarily on various forms of immunosuppression which carry potentially severe side effects and often lose effectiveness overtime. Given this, new forms of therapy are needed. We propose small-interfering RNA (siRNA) for hypervariable regions of the T-cell receptor β-chain gene (TCRb) as a highly targeted, novel means of therapy for the treatment of autoimmune disorders.

Objectives:

To develop methods to produce siRNA targeting …

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …

Prophylaxis Of Food Allergen Sensitivity, Dustin Gottfeld

Physician Assistant Studies | Student Authored Articles

Food allergies can have a severe and drastic effect on a person’s lifestyle, while prevention of allergic disease can help to ensure others do not have to live with this burden. There are a variety of differing hypotheses that offer explanations for the early development of food allergies, particularly peanut allergies. Two of the foremost hypotheses are the Hygiene Hypothesis and the Dual-Allergen Hypothesis. The Hygiene Hypothesis claims that the diversity of a child’s microbiota creates a beneficial balance of microorganisms which can help prevent the development of allergic disease. Alternatively, the Dual-Allergen Hypothesis states that early environmental exposure to …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Elucidating The Complex Signaling Events Driving Intestinal Stem Cell Plasticity Following Injury, Evan Lynch

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Signaling events governing intestinal stem cell (ISC) homeostasis maintain the delicate balance of active self-renewal and passive differentiation to replenish intestinal epithelial cells (IEC) every 3-5 days. However, under certain contexts, ISC function is irreversibly compromised—requiring committed IEC lineages to dedifferentiate and regain “stemness”. In the current studies, we examine the signaling events driving epithelial cell responses to injury to expose pathologic failures in the healing response. Our specific goal is to tease out the cellular contexts that promote dedifferentiation to design effective therapeutics for disease conditions compromising ISC function.

First, we generated a novel transgenic animal using the epithelial-specific …

Super Learner Analysis Of Real-Time Electronically Monitored Adherence To Antiretroviral Therapy Under Constrained Optimization And Comparison To Non-Differentiated Care Approaches For Persons Living With Hiv In Rural Uganda, Alejandra E. Benitez, Nicholas Musinguzi, David Bangsberg, Mwebesa B. Bwana, Conrad Muzoora, Peter Hunt, Jeffrey N. Martin, Jessica E. Haberer, Maya L. Petersen

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction

Real‐time electronic adherence monitoring (EAM) systems could inform on‐going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real‐time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches.

Methods

We evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real‐time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, …