Immune System Diseases Commons^™

Nanomedicine For Immunosuppressive Therapy: Achievements In Pre-Clinical Research, Hanan Al-Lawati, Hamidreza Montazeri Aliabadi, Behzad Sharif Makhmalzadeh, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Introduction: Immunosuppression is the mainstay therapy in organ transplantation and autoimmune diseases. The effective clinical application of immunosuppressive agents has suffered from the emergence of systemic immunosuppression and/or individual drug side effects. Nanotechnology approaches may be used to modify the mentioned shortcomings by enhancing the delivery of immunosuppressants to target cells of the immune system, thus reducing the required dose for function, and/or reducing drug distribution to non-target tissues.

Areas covered: We provide an overview on the development of nanotechnology products for the most commonly used immunosuppressive agents. At first, the rationale for the use of nanoparticles as …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Vista Deficiency Attenuates Antibody-Induced Arthritis And Alters Macrophage Gene Expression In Response To Simulated Immune Complexes, Sabrina Ceeraz, Susan K. Eszterhas, Petra Sergent, David A. Armstrong, Alix Ashare, Thomas Broughton, Li Wang, Dov Pechenick, Christopher M. Burns, Randolph J. Noelle, Matthew P. Vincenti, Roy A. Fava

Dartmouth Scholarship

In addition to activated T cells, the immune checkpoint inhibitor “V domain-containing Ig suppressor of T-cell activation” (VISTA) is expressed by myeloid cell types, including macrophages and neutrophils. The importance of VISTA expression by myeloid cells to antibody-induced arthritis and its potential for relevance in human disease was evaluated. Methods: VISTA was immunolocalized in normal and arthritic human synovial tissue sections and synovial tissue lysates were subjected to western blot analysis. The collagen antibody-induced arthritis model (CAIA) was performed with DBA/1 J mice treated with antibodies against VISTA and with VISTA-deficient mice (V-KO). Total mRNA from arthritic joints, spleens, and …

Clinical And Serological Features Of Systemic Sclerosis In A Multicenter African American Cohort: Analysis Of The Genome Research In African American Scleroderma Patients Clinical Database, Nadia Morgan, Ami Shah, Maureen Mayes, Robyn Domsic, Thomas Medsger, Victoria K. Shanmugam, +Several Additional Authors

Medicine Faculty Publications

Racial differences exist in the severity of systemic sclerosis (SSc). To enhance our knowledge about SSc in African Americans, we established a comprehensive clinical database from the largest multicenter cohort of African American SSc patients assembled to date (the Genome Research in African American Scleroderma Patients (GRASP) cohort).

African American SSc patients were enrolled retrospectively and prospectively over a 30-year period (1987–2016), from 18 academic centers throughout the United States. The cross-sectional prevalence of sociodemographic, clinical, and serological features was evaluated. Factors associated with clinically significant manifestations of SSc were assessed using multivariate logistic regression analyses.

The study population included …

Activation Des Éosinophiles Humains Par Des Nanoparticules, Denis Girard, Maxime Marion-Murphy

Rapports de recherche scientifique

L’économie du Canada, comme celle de bien d’autres pays industrialisés, bénéficie du développement des nanotechnologies dont le fort potentiel peut être exploité dans plusieurs secteurs industriels. Un nombre croissant d’entreprises québécoises de production de nanoparticules (NP) est d’ailleurs déjà implanté et tout porte à croire que d’autres emboîteront le pas dans les années à venir. Ce faisant, non seulement le nombre de travailleurs œuvrant dans la fabrication et la synthèse des NP augmentera sensiblement, mais également le nombre de ceux qui seront appelés à en manipuler et à en transformer dans les domaines des nanotechnologies en général. Une des conséquences …

Dftd Age Structure And Vaccination Modeling, Christopher D. Bruno

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Mathematical Medicine: Modeling Disease And Treatment, Lisette Depillis

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty and Staff Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

Suppression Of Chrn Endocytosis By Carbonic Anhydrase Car3 In The Pathogenesis Of Myasthenia Gravis, Ailian Du, Shiqian Huang, Xiaonan Zhao, Kuan Fang, Shuangyan Zhang, Jiefang Huang, Xiang Miao, Fulvio Baggi, Rennolds S. Ostrom, Yanyun Zhang, Xiangjun Chen, Congfeng Xu

Pharmacy Faculty Articles and Research

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/ AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN …

A Roundtable On Cross-Sector Collaboration And Resource Alignment For Health Equity: Meeting Summary, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

Cross-sector collaboration is a highly recommended strategy to eliminate health inequities nationally and globally. In the federal sector, it is evolving into an important approach for solving complex social problems, as evidenced by its steady proliferation the past few decades. Despite the increased adoption of cross-sector collaboration, it is still not a default strategy or preeminent option for managing complex social problems. In September 2015, the Federal Interagency Health Equity Team (FIHET) hosted a Roundtable event to discuss opportunities and strategies to foster widespread adoption of cross-sector collaboration and resource alignment. The Roundtable featured several expert panelists and participants from …

An Assessment Of Funding And Other Capacity Needs For Health Equity Programming Within State-Level Chronic Disease Programs, Tiffany Pertillar, Ann Pobutsky, Phd, Gail Brandt, Edd, Mph, Marisa New, Otr, Mph, Jamielou Delavan, Ba, Robyn Taylor, Mba, Amishi Shah, Mpa, Ma, Folasaya Adunola, Dds, Mph, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

Background: Chronic diseases are an important contributor to morbidity and mortality among racial/ethnic minority, low-income, and other under-resourced populations. Given that state health departments (and their chronic disease programs) play a significant role in providing population and preventive health services, their capacity to promote health equity is an important consideration in national efforts to address chronic diseases. The purpose of this study was to examine capacity needs of state chronic disease programs with respect to promoting health equity.

Methods: In 2015, the National Association of Chronic Disease Directors (NACDD) conducted a survey of its members that work within a …

Achieving Health Equity For Indian Country, Jamie Ishcomer

Journal of Health Disparities Research and Practice

The essence of health equity is giving resources where they are needed most. American Indians and Alaska Natives (AI/AN) continue to have the worst health outcomes, live in some of the most desperate of conditions, and lack access to even basic amenities that many other Americans could not survive without. Although Tribes have been plagued with social, economic and political injustice for centuries, there is an opportunity to put a stop to the systematic oppression and build up the first peoples of this country. A partnership between the National Indian Health Board (NIHB) and the National Partnership for Action to …

Rhode Island’S Health Equity Zones: Addressing Local Problems With Local Solutions, Nicole Alexander-Scott, Md, Mph, Ana P. Novais, Ma, Carol Hall-Walker, Mpa, Angela B. Ankoma, Mph, Msw, John P. Fulton, Phd

Journal of Health Disparities Research and Practice

The Rhode Island Department of Health (RIDOH) describes the strategies and infrastructure it has developed to fund its placed-based initiatives to address the social determinants of health to eliminate health disparities. Using a data driven and community-led approach, RIDOH funded 10 local collaboratives, each with its own, geographically-defined “Health Equity Zone,” or “HEZ,” and, to support the collaboratives, created a new “Health Equity Institute,” a “HEZ Team” of 9 seasoned project managers, and direct lines of communications between these assets and the Office of the Director of Health.

Implementation Of The National Partnership For Action To End Health Disparities: A Three-Year Retrospective, Oscar Espinosa, Brandon Coffee-Borden, Mpp Coffee-Borden, Mpp, Alexis Bakos, Phd, Mph, Rn, D. Bakos, Phd, Mph, Rn, Onyemaechi Nweke

Journal of Health Disparities Research and Practice

In April 2011, the U.S. Department of Health and Human Services’ (HHS) Office of Minority Health (OMH) launched the National Partnership for Action to End Health Disparities (NPA) to increase the effectiveness of efforts to eliminate health disparities by coordinating partners, leaders, and stakeholders committed to action. At its core, the NPA is an experiment in collaboration that relies heavily on those on the front line who are actively engaged in minority health work at multiple levels. It gives them the responsibility of identifying and helping to define core actions, new approaches, and new partnerships that ultimately will help to …

The Guide To Community Preventive Services Review Of Interventions To Promote Health Equity In The United States, Robert Hahn, Jonathan E. Fielding, M.D., M.P.H., M.A., M.B.A, Robert L. Johnson, M.D., Carles Muntaner, M.D., Ph.D., M.H.S., Benedict I. Truman, M.D., M.P.H., Tracy Orleans

Journal of Health Disparities Research and Practice

The optimal approach to eliminating health inequities is through evidence-based interventions. In 2009, the non-federal Community Preventive Services Task Force launched a series of systematic reviews of interventions to promote health equity. Topics to be considered include education, employment, housing, and transportation. Thus far, reviews have focused on educational interventions: center-based early childhood education, full-day kindergarten programs, out-of-school time academic programs, high school completion programs, and school-based health centers. These reviews demonstrate the benefits of diverse educational interventions in advancing health equity. Here, we summarize the strategy of Community Guide health equity reviews, first findings and challenges.

Multiple Myeloma Baseline Immunoglobulin G Level And Pneumococcal Vaccination Antibody Response, Michael A. Thompson, Martin K. Oaks, Maharaj Singh, Karen M. Michel, Michael P. Mullane, Husam S. Tarawneh, Angi Kraut, Kayla J. Hamm

Journal of Patient-Centered Research and Reviews

Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. Vaccination clinical efficacy endpoints have not been demonstrated, and there are limited data on surrogate markers of efficacy. This pilot study evaluated sequential immunologic markers after standard pneumococcal vaccination (PV) in patients with MM and non-MM controls. Vaccination was standard for PV (PCV13 or PPV23), with laboratory testing at baseline and at 2, 4, 12 and 24 weeks after vaccination. Immunoglobulin G (IgG) antibodies to pneumococcal antigens were detected by ELISA. Prevaccination total IgG levels and IgG subclass levels were also …

Extrafollicular Activities: Perspectives On Hiv Infection, Germinal Centerindependent Maturation Pathways, And Kshv-Mediated Lymphoproliferation, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Early events in the pathogenesis of KSHV-associated lymphoproliferations in the context of HIV disease remain poorly understood. Recent research indicates that latent HIV infection causes persistent immune dysfunction in B cell follicles. Simultaneously, lack of T cell immune surveillance in the lymph nodes dysregulates the biology of EBV. In sum, these defects bias B lymphocyte maturation away from traditional T cell-dependent germinal center-mediated pathways and towards extrafollicular pathways. Recent advances in B lymphocyte immunology suggest that extrafollicular maturation pathways for antibody secreting cells are more flexible and robust than previously believed. These responses are now understood to be both durable …

Risk For Cardiovascular Disease In Blacks With Hiv/Aids In America: A Systematic Review And Meta-Analysis, Calvin Odhiambo, Jessica Davis, Bernard Omolo

Journal of Health Disparities Research and Practice

Cardiovascular disease (CVD) related to HIV infection is becoming a major public health concern in the United Stated. Epidemiologic studies show that prolonged use of Highly Active Antiretroviral Therapy, HIV/AIDS itself, and a combination of traditional vascular risk factors increase the risk for CVD among people with HIV/AIDS. However, little is known about any racial disparities in the risk for CVD in the HIV/AIDS population. We conducted a systematic review and meta-analysis of literature on HIV/AIDS and CVD (June 1, 2010-July 31, 2014) through MEDLINE to examine whether and how HIV-positive African Americans are disproportionately affected by CVD compared to …

Immune Checkpoint Inhibition And The Prevalence Of Autoimmune Disorders Among Patients With Lung And Renal Cancer, Sherif M. El-Refai

Pharmaceutical Sciences Faculty Publications

PURPOSE: Immune checkpoint inhibition reactivates the immune response against cancer cells in multiple tissue types and has been shown to induce durable responses. However, for patients with autoimmune disorders, their conditions can worsen with this reactivation. We sought to identify, among patients with lung and renal cancer, how many harbor a comorbid autoimmune condition and may be at risk of worsening their condition while on immune checkpoint inhibitors such as nivolumab and pembrolizumab.

METHODS: An administrative health care claims database, Truven MarketScan, was used to identify patients diagnosed with lung and renal cancer from 2010 to 2013. We assessed patients …

The Severity And Lack Of Awareness Of Dermatomyositis, Alexander Lorenzo Perez Herrera

Senior Theses

Dermatomyositis is a rare autoimmune disease that affects a very small percentage of the population, close to 10 cases per million, according to the National Organization of Rare Disorders (NORD). The amount of men that are diagnosed with this disease are even smaller. However, hardly anyone knows what Dermatomyositis is, let alone what its side effects are. The purpose of this research paper is to exploit the severity of Dermatomyositis for those who are unaware of its existence, characteristics and significance within the health community. In doing so, I hope to create awareness throughout society by also telling my father’s …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

A Comparative Analysis Of The West African Hemorrhagic Fevers Caused By The Lassa And Ebola Viruses, Emiene E. Amali-Adekwu

Selected Honors Theses

Lassa fever (LF) and Ebola Hemorrhagic Fever (EHF) are viral diseases endemic to West Africa.The etiological agent of Lassa fever is an enveloped virus from the Arenaviridae family and was first discovered in 1969 when two missionary nurses died of a mysterious illness in the town of Lassa in Borno state, Nigeria.1 This virus is animal-borne (zoonotic) and is carried by the animal vector Mastomys natalensis (multimammate rat). The Ebola virus is also zoonotic originating from fruit bats belonging to the Pteropodidae family.2 The first reported case of Ebola Virus Disease (EVD) was a principal who was believed to have …

A Review Of Ankylosing Spondylitis, Hannah L. Owen

Senior Honors Theses

Ankylosing spondylitis (AS) is a systemic autoimmune disorder that induces ankylosis of the spine (fusion of the vertebrae at their various joints) and inflammatory arthritis of peripheral joints among other symptoms. Overexpression of cytokines, the presence of genetic mutations not exclusive to the human leucocyte antigen (HLA)-B27 region, and environmental factors all have large roles in the progressive development of AS. Although a definitive pathology continues to be sought after, researchers believe the adaptive immune system in AS patients attacks fibrocartilaginous entheses (supportive connective tissue between bone and attached structures like tendon, ligament, and fascia).

AS markedly reduces proper systemic …

Beyond Skin Deep: The Traumatic Effects Of Dermatomyositis, Alexander Lorenzo Perez Herrera

Scholarly and Creative Works Conference (2015 - 2021)

Dermatomyositis is a rare autoimmune disease that affects a very small percentage of the population, close to 10 cases per million, according to the National Organization of Rare Disorders (NORD). The amount of men that are diagnosed with this disease are even smaller. However, hardly anyone knows what Dermatomyositis is, let alone what its side effects are. The purpose of this research paper is to exploit the severity of Dermatomyositis for those who are unaware of its existence, characteristics and significance within the health community. In doing so, I hope to create awareness throughout society by also telling my father’s …

Novel Genetic Variants Associated With Child Refractory Esophageal Stricture With Food Allergy By Exome Sequencing., Min Yang, Min Xiong, Huan Chen, Lanlan Geng, Peiyu Chen, Jing Xie, Shui Qing Ye, Ding-You Li, Sitang Gong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets.

METHODS: To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy.

RESULTS: A total of 91,024 variants were identified. By filtering out 'normal variants' against those of the 1000 Genomes Project, we identified 12,741 remaining variants which are potentially associated with RES plus …

A Novel Multi-Network Approach Reveals Tissue-Specific Cellular Modulators Of Fibrosis In Systemic Sclerosis, Jaclyn N. Taroni, Casey S. Greene, Viktor Martyanov, Tammara A. Wood

Dartmouth Scholarship

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology.We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast …

Pulmonary Surfactant Fortified With Cath-2 As A Novel Therapy For Bacterial Pneumonia, Brandon J. Baer

Western Research Forum

Background: Bacterial pneumonia is a leading cause of death worldwide, with high mortality rates persisting even after antibiotic treatment. Current treatments for pneumonia involve administration of antibiotics, however after the bacteria are killed they release toxic substances that induce inflammation and lung dysfunction. Host defense peptides represent a potential solution to this problem through their ability to down regulate inflammation. However, effective delivery to the lung is difficult because of the complex branching structure of the airways. My study addresses this delivery problem by using exogenous surfactant, a pulmonary delivery vehicle capable of improving spreading of these peptides throughout the …

Improving Antiretroviral Therapy Adherence In Resource-Limited Settings At Scale: A Discussion Of Interventions And Recommendations, Jessica E. Haberer, Lora Sabin, K. Rivet Amico, Catherine Orrell, Omar Galarraga, Alexander C. Tsai, Rachel C. Vreeman, Ira Wilson, Nadia A. Sam-Agudu, Terrence F. Blaschke, Bernard Vrijens, Claude Mellins, Robert H. Remien, Sheri D. Weiser, Elizabeth Lolwenthal, Michael J. Stirratt, Papa Salif Sow, Bruce Thomas, Nathan Ford, Edward Mills, Richard Lester, Jean B. Nachega, Bosco M. Bwana, Fred Ssewamala, Lawrence Mbuagbaw, Paula Munderi, Elvin H. Geng, David Bangsberg

OHSU-PSU School of Public Health Faculty Publications and Presentations

INTRODUCTION:

Successful population-level antiretroviral therapy (ART) adherence will be necessary to realize both the clinical and prevention benefits of antiretroviral scale-up and, ultimately, the end of AIDS. Although many people living with HIV are adhering well, others struggle and most are likely to experience challenges in adherence that may threaten virologic suppression at some point during lifelong therapy. Despite the importance of ART adherence, supportive interventions have generally not been implemented at scale. The objective of this review is to summarize the recommendations of clinical, research, and public health experts for scalable ART adherence interventions in resource-limited settings.

METHODS:

In …

Vaccine Coverage And Adherence To Epi Schedules In Eight Resource Poor Settings In The Mal-Ed Cohort Study, Christel Hoest, Jessica C. Seidman, Gwenyth Lee, James A. Platts-Mills, Syed Asad Ali, Maribel Paredes Olortegui, Pascal Bessong, Ram Chandyo, Sudhir Babji, Venkata Raghava Mohan

Department of Paediatrics and Child Health

Background: Launched in 1974, the Expanded Program on Immunization (EPI) is estimated to prevent two-three million deaths annually from polio, diphtheria, tuberculosis, pertussis, measles, and tetanus. Additional lives could be saved through better understanding what influences adherence to the EPI schedule in specific settings.
Methods: The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study followed cohorts in eight sites in South Asia, Africa, and South America and monitored vaccine receipt over the first two years of life for the children enrolled in the study. Vaccination histories were obtained …

Epigenetic Silencing Of Socs3 Expression Contributes To Fibrosis In Crohn’S Disease, Emily T. Marshall, Chao Li, John K. Kuemmerle

MD Student Summer Research Fellowship Program Posters

Identified risk polymorphisms affecting the Jak-STAT3 pathway in patients with Crohn’s disease could affect TGF-β1 and collagen I expression and in the pathway’s negative regulator, SOCS3. Genetic factors, however, account for only ~25% of disease. Epigenetic events also shape gene expression. Recent experiments showed that autocrine IL-6 production in mesenchymal cells, subepithelial myofibroblasts (SEMF) and muscle cells, of patients with fibrostenotic Crohn’s disease causes sustained Jak-STAT3 activity, excess TGF-β1 and Collagen I production and fibrosis. SOCS3 paradoxically decreased in these cells. We now identify epigenetic mechanisms that silence SOCS3 expression in SEMF of patients with fibrostenotic Crohn’s disease. In a …