Immune System Diseases Commons^™

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …

A Case Series Of Unusual Iga Vasculitis, Jared Bradley, Ian Whitaker, Brittany Lyons, Amy Mangla

HCA Healthcare Journal of Medicine

Introduction

Immunoglobulin A vasculitis (IgA)is a rare condition characterized by palpable purpura, often involving the skin, gastrointestinal tract, joints, and kidneys. Presentation is usually acute and is more common in children and adolescents of Southeast Asian and European descent. In the adult population, it is less common and therapies are not as well-established.

Case Presentation

Disease prevalence of IgA vasculitis outside Southeast Asian and European populations is not well-documented. In this case series, we present 2 cases of IgA vasculitis in 2 older adult males, one of Native American descent and one of African American descent.

Conclusion

IgA vasculitis must …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

D-Mannose Reduces Cellular Senescence And Nlrp3/Gasdermind/Il-1Β-Driven Pyroptotic Uroepithelial Cell Shedding In The Murine Bladder, Chetanchandra S Joshi, Arnold M Salazar, Caihong Wang, Marianne M Ligon, Rayvanth R Chappidi, Bisiayo E Fashemi, Paul A Felder, Amy Mora, Sandra L Grimm, Cristian Coarfa, Indira U Mysorekar

Faculty, Staff and Students Publications

Aging is a risk factor for disease via increased susceptibility to infection, decreased ability to maintain homeostasis, inefficiency in combating stress, and decreased regenerative capacity. Multiple diseases, including urinary tract infection (UTI), are more prevalent with age; however, the mechanisms underlying the impact of aging on the urinary tract mucosa and the correlation between aging and disease remain poorly understood. Here, we show that, relative to young (8-12 weeks) mice, the urothelium of aged (18-24 months) female mice accumulates large lysosomes with reduced acid phosphatase activity and decreased overall autophagic flux in the aged urothelium, indicative of compromised cellular homeostasis. …

Features Of Acute Covid-19 Associated With Post-Acute Sequelae Of Sars-Cov-2 Phenotypes: Results From The Impacc Study, Al Ozonoff, Naresh Doni Jayavelu, Shanshan Liu, Esther Melamed, Carly E Milliren, Jingjing Qi, Linda N Geng, Grace A Mccomsey, Charles B Cairns, Lindsey R Baden, Joanna Schaenman, Albert C Shaw, Hady Samaha, Vicki Seyfert-Margolis, Florian Krammer, Lindsey B Rosen, Hanno Steen, Caitlin Syphurs, Ravi Dandekar, Casey P Shannon, Rafick P Sekaly, Lauren I R Ehrlich, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Harm Van Bakel, Seunghee Kim-Schulze, David A Hafler, Ofer Levy, Monica Kraft, Chris Bime, Elias K Haddad, Carolyn S Calfee, David J Erle, Charles R Langelier, Walter Eckalbar, Steven E Bosinger, Bjoern Peters, Steven H Kleinstein, Elaine F Reed, Alison D Augustine, Joann Diray-Arce, Holden T Maecker, Matthew C Altman, Ruth R Montgomery, Patrice M Becker, Nadine Rouphael

Faculty, Staff and Students Publications

Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B …

A Rare Case Of Cold Agglutination Syndrome Secondary To Mycoplasma Pneumoniae, Dr.Disha Shahri, Dr. Srinath K. M, Dr. Basava Chethan, Dr. Savitha Vijayakumar, Dr. Meghna B.S.

Digital Journal of Clinical Medicine

Mycoplasma pneumoniae (M. pneumoniae) is one of the foremost causes of community acquired pneumonia. Most of the cases are, however mild. Although, complications may seldom occur. One such known complication of M. pneumoniae infection is cold agglutinin hemolysis, which is usually benign and transient. This hemolysis is due to formation of cold agglutinins during the course of infection. Cold Agglutination Syndrome (CAS) is a type of acquired Autoimmune Hemolytic Anaemia (AIHA), which exists due to an underlying disorder, like a viral illness or lymohoid malignancy. It is generally self-remitting, in contrast to Cold Agglutination Disease (CAD), which is a chronic …

A Case Report Navigating Cvid And Sarcoidosis Overlaps In Pediatric Nephritis, Amanda Salih, Amanda Brown, Amanda Grimes, Sana Hasan, Manuel Silva-Carmona, Leyat Tal, Joud Hajjar

Faculty, Staff and Students Publications

Common variable immunodeficiency (CVID) can be complicated by granulomatous disease, often granulomatous lymphocytic interstitial lung disease (GLILD). Granulomatous interstitial nephritis represents an atypical presentation in pediatrics. Our patient is a previously healthy 13-year-old white male with a recent diagnosis of CVID. He presented with a rash and laboratory findings included pancytopenia (white blood cells 2.6 cells × 103/μl, hemoglobin 11.8 g/dl, platelets 60 × 103/μl), hypercalcemia (14.9 mg/dl), elevated Vit D 1,25 OH level (>200 pg/ml), hyperuricemia (8.8 mg/dl), and acute kidney injury (AKI) (serum creatinine 1.1 mg/dl; baseline 0.64 mg/dl). A broad infectious workup was unremarkable. The rash …

Assessment Of Deficits In Specific Cognitive Domains In Older Adults Living With Hiv., Andrea Reyes-Vega, Harideep Samanapally, Rishikesh Rijal, Stephen P. Furmanek, Christopher B. Shields, Brandon C. Dennis, Smita Ghare, Shirish Barve

Faculty and Staff Scholarship

A significant proportion of people living with HIV (PLWH) have cognitive impairment. Moreover, approximately 70% of PLWH in the United States will be ≥50 years old by 2030, raising concerns of a higher incidence of dementia as they age. Accordingly, there is a clinical need to monitor their cognitive status. The aim of this study was to delineate specific cognition areas impacted in OALWH with a clinical diagnosis of neurocognitive impairment. We used a comprehensive set of tests (paper and NIH Toolbox Cognition Battery), to assess different cognitive domains in a total of 25 OALWH ≥ 50 years. 64% were …

Citrullinated And Malondialdehyde-Acetaldehyde Modified Proteins Promote Cellular Inflammatory And Fibrotic Responses Associated With Rheumatoid Arthritis, Nozima Aripova

Theses & Dissertations

Rheumatoid arthritis (RA) is a systemic, autoimmune disease primarily characterized by perpetual synovial inflammation that results in synovial tissue proliferation and fibrosis (pannus). Although joint involvement is the predominant manifestation of RA, extra-articular features, such as interstitial lung disease (ILD), contribute significantly to the elevated mortality associated with the condition. Post-translational modifications play a significant role in RA and RA-ILD pathogenesis. Circulating anti-citrullinated protein antibodies (ACPAs) are a highly diagnostic tool implicating a potential role for citrullinated antigens in RA and RA-ILD.

Recently, antibodies to malondialdehyde acetaldehyde adducts (MAA) have been markedly elevated in patients with RA and RA-ILD. MAA …

The Dna Glycosylase Neil2 Is Protective During Sars-Cov-2 Infection, Nisha Tapryal, Anirban Chakraborty, Kaushik Saha, Azharul Islam, Lang Pan, Koa Hosoki, Ibrahim M Sayed, Jason M Duran, Joshua Alcantara, Vanessa Castillo, Courtney Tindle, Altaf H Sarker, Maki Wakamiya, Victor J Cardenas, Gulshan Sharma, Laura E Crotty Alexander, Sanjiv Sur, Debashis Sahoo, Gourisankar Ghosh, Soumita Das, Pradipta Ghosh, Istvan Boldogh, Tapas K Hazra

Faculty, Staff and Students Publications

SARS-CoV-2 infection-induced aggravation of host innate immune response not only causes tissue damage and multiorgan failure in COVID-19 patients but also induces host genome damage and activates DNA damage response pathways. To test whether the compromised DNA repair capacity of individuals modulates the severity of COVID-19 infection, we analyze DNA repair gene expression in publicly available patient datasets and observe a lower level of the DNA glycosylase NEIL2 in the lungs of severely infected COVID-19 patients. This observation of lower NEIL2 levels is further validated in infected patients, hamsters and ACE2 receptor-expressing human A549 (A549-ACE2) cells. Furthermore, delivery of recombinant …

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer’S Disease: Research Outline And Call For Collaboration, Richard Lathe, Nikki M Schultek, Brian J Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi, Intracell Research Group Consortium Collaborators

Faculty, Staff and Students Publications

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

Toll-Like Receptor 4 And Cd11b Expressed On Microglia Coordinate Eradication Of Candida Albicans Cerebral Mycosis, Yifan Wu, Shuqi Du, Lynn H Bimler, Kelsey E Mauk, Léa Lortal, Nessim Kichik, James S Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P Richardson, Bernhard Hube, Julian R Naglik, David B Corry

Faculty, Staff and Students Publications

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. …

Loss Of Stearoyl-Coa Desaturase 2 Disrupts Inflammatory Response In Macrophages, Joseph B Lin, Amy Mora, Tzu Jui Wang, Andrea Santeford, Darksha Usmani, Marianne M Ligon, Indira U Mysorekar, Rajendra S Apte

Faculty, Staff and Students Publications

Macrophages are innate immune cells that patrol tissues and are the first responders to detect infection. They orchestrate the host immune response in eliminating invading pathogens and the subsequent transition from inflammation to tissue repair. Macrophage dysfunction contributes to age-related pathologies, including low-grade inflammation in advanced age that is termed "inflammaging." Our laboratory has previously identified that macrophage expression of a fatty acid desaturase, stearoyl-CoA desaturase 2 (SCD2), declines with age. Herein, we delineate the precise cellular effects of SCD2 deficiency in murine macrophages. We found that deletion of

Performance Of A Modified Fracture Risk Assessment Tool For Fragility Fracture Prediction Among Older Veterans Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Farah Kidwai-Khan, Melissa Skanderson, Thomas M Gill, Barbara Gulanski, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Evelyn Hsieh

Faculty, Staff and Students Publications

OBJECTIVE: Fragility fractures (fractures) are a critical outcome for persons aging with HIV (PAH). Research suggests that the fracture risk assessment tool (FRAX) only modestly estimates fracture risk among PAH. We provide an updated evaluation of how well a 'modified FRAX' identifies PAH at risk for fractures in a contemporary HIV cohort.

DESIGN: Cohort study.

METHODS: We used data from the Veterans Aging Cohort Study to evaluate veterans living with HIV, aged 50+ years, for the occurrence of fractures from 1 January 2010 through 31 December 2019. Data from 2009 were used to evaluate the eight FRAX predictors available to …

Extrinsic Allergic Alveolitis: A Systematic Review Of Hla-Dr In Pigeon Breeder’S Disease, Dylan Thibaut, Ryan A. Witcher, Anitha Kunnath, James Toldi

Advances in Clinical Medical Research and Healthcare Delivery

Abstract

Introduction: Pigeon Breeder’s Pneumonitis (PBP) results due to a complex pathophysiology that includes exposure to avian antigens. Susceptibility has been linked to human leukocyte antigen (HLA) class II, though consensus has not been reached. The goal of this systematic review is to further elucidate the association between PBP and HLA-DR subtypes.

Methods: Databases utilized included PubMed, Google Scholar, ScienceDirect, and Cochrane Library. Inclusion required a minimum of three studies in English presenting HLA-DR alleles of PBP and control subgroups. Exclusion was due to insufficient data or non-feasible control groups. Forest plots were created for HLA-DR subtypes’ association …

Assessing The Contributions Of Modifiable Risk Factors To Serious Falls And Fragility Fractures Among Older Persons Living With Hiv, Julie A Womack, Terrence E Murphy, Linda Leo-Summers, Jonathan Bates, Samah Jarad, Thomas M Gill, Evelyn Hsieh, Maria C Rodriguez-Barradas, Phyllis C Tien, Michael T Yin, Cynthia A Brandt, Amy C Justice

Faculty, Staff and Students Publications

BACKGROUND: Although 50 years represents middle age among uninfected individuals, studies have shown that persons living with HIV (PWH) begin to demonstrate elevated risk for serious falls and fragility fractures in the sixth decade; the proportions of these outcomes attributable to modifiable factors are unknown.

METHODS: We analyzed 21,041 older PWH on antiretroviral therapy (ART) from the Veterans Aging Cohort Study from 01/01/2010 through 09/30/2015. Serious falls were identified by Ecodes and a machine-learning algorithm applied to radiology reports. Fragility fractures (hip, vertebral, and upper arm) were identified using ICD9 codes. Predictors for both models included a serious fall within …

Maackia Amurensis Seed Lectin (Masl) Increases Movement Velocity Of Mice With Tnfα Induced Rheumatoid Arthritis, Amanda A. Greenspan, Kelly L. Hamilton, Alan J. Shienbaum, Bradford Fischer, Andrea Bottaro, Gary S. Goldberg

Rowan-Virtua Research Day

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN …

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

Uncovering Novel Mechanism Of Immune Modulation Of Invariant Natural Killer T Cells By Liposomal Α-Galactosylceramide, Alexandra S. Flegle

Dissertations and Theses (Open Access)

Invariant Natural Killer T cells (iNK-T cells) are a powerful regulatory immune cell that can recruit both innate and adaptive immune cells. Unlike conventional T cells (CD4⁺ and CD8α⁺), they recognize glycolipid antigens via the MHC-class-I like molecule, CD1d. A synthetically derived glycolipid from the marine sponge, Agelas mauritianus, alpha-Galactosylceramide (α-GalCer) potently activates iNK-T cells. Within a few hours after activation, iNK-T cells produce high quantities of T_H1 and T_H2 type cytokines, thus shape subsequent adaptive immunity towards inflammation (T_H1) or immune-suppression (T_H2). Structural modification of α-GalCer’s phytosphingosine …

Bladder Mucosal Cystitis Cystica Lesions Are Tertiary Lymphoid Tissues That Correlate With Recurrent Urinary Tract Infection Frequency In Postmenopausal Women, Marianne M Ligon, Brooke Liang, Stacy M Lenger, Priyanka Parameswaran, Siobhan Sutcliffe, Jerry L Lowder, Indira U Mysorekar

Faculty, Staff and Students Publications

PURPOSE: We identify correlates and clinical outcomes of cystitis cystica, a poorly understood chronic inflammatory bladder change, in women with recurrent urinary tract infections.

MATERIALS AND METHODS: A retrospective, observational cohort of women with recurrent urinary tract infections who underwent cystoscopy (n=138) from 2015 to 2018 were identified using electronic medical records. Cystitis cystica status was abstracted from cystoscopy reports and correlations were identified by logistic regression. Urinary tract infection-free survival time associated with cystitis cystica was evaluated by Cox proportional hazards regression. Exact logistic regression was used to identify factors associated with changes to cystitis cystica lesions on repeat …

Contribution Of Adaptive Immunity To Human Copd And Experimental Models Of Emphysema, Farrah Kheradmand, Yun Zhang, David B Corry

Faculty, Staff and Students Publications

The pathophysiology of chronic obstructive pulmonary disease (COPD) and the undisputed role of innate immune cells in this condition have dominated the field in the basic research arena for many years. Recently, however, compelling data suggesting that adaptive immune cells may also contribute to the progressive nature of lung destruction associated with COPD in smokers have gained considerable attention. The histopathological changes in the lungs of smokers can be limited to the large or small airways, but alveolar loss leading to emphysema, which occurs in some individuals, remains its most significant and irreversible outcome. Critically, however, the question of why …

Role Of Biomarkers (Sflt-1/Plgf) In Cases Of Covid-19 For Distinguishing Preeclampsia And Guiding Clinical Management, Guilherme M Nobrega, Jose P Guida, Juliana M Novaes, Larissa M Solda, Luciana Pietro, Adriana G Luz, Giuliane J Lajos, Carolina C Ribeiro-Do-Valle, Renato T Souza, Jose G Cecatti, Indira U Mysorekar, Tabata Z Dias, Maria Laura Costa

Faculty, Staff and Students Publications

OBJECTIVES: To analyze soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factors (PlGF) concentrations and their ratio in pregnant and postpartum women with suspected COVID-19, and further investigate conditions associated with an increased ratio (sFlt-1/PlGF > 38), including preeclampsia (PE) and severe acute respiratory syndrome (SARS).

STUDY DESIGN: The present study is a secondary analysis of a prospective cohort. Blood samples were collected at time of COVID-19 investigation and the serum measurements of sFlt-1 and PlGF were performed. Clinical background, SARS-CoV-2 infection characteristics, maternal and perinatal outcomes were further analyzed.

MAIN OUTCOME MEASURES: Serum measurements of sFlt-1 and PlGF; obstetrics …

Vitamin C Contributes To Epigenetic Regulation Of Genes Related To Diabetic Retinopathy In Retinal Endothelial Cells, Elizabeth L. Turner, Jonathon Reynolds, Walker Kay, Marianne Becnel, Matthew Conway, Alexander Kim, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Relative Adrenal Insufficiency In Sepsis, Dan Hao

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBI^fl/fl mice as the first …

Vitamin D Enhanced Vitamin D Receptor (Vdr) Inhibition Of Nlrp3 Inflammasome Activation Can Attenuate The Development Of Autoimmune Thyroiditis, Alexzon Mandac

Capstone Showcase

Autoimmune Thyroiditis (AIT) is a prevalent autoimmune disease affecting approximately 2% of the population. Characterized by the gradual loss of thyroid function through an autoimmune attack on the thyroid gland, the disease manifests symptoms that negatively affect one’s quality of life. The mechanisms behind the disease’s pathophysiology are not fully understood; however, researchers are examining the involvement of the NLRP3 inflammasome in the disease. This thesis will address the question of whether Vitamin D can act as an inhibitor of the NLRP3 inflammasome and attenuate the progression of AIT in mouse model. Current investigations explore the effects of NLRP3 inhibition …