Medical Immunology Commons^™

Literature Review Of Stiff Person Syndrome, Mustafa Ansari, Adam Davis, Donald Penney

The Journal of Integrated Primary Care

Background: Stiff Person Syndrome (SPS) is a rare, debilitating autoimmune neurological disorder characterized by progressive muscle rigidity, painful spasms, and gait disturbances. It is strongly associated with autoantibodies against glutamic acid decarboxylase (GAD), leading to impaired GABAergic neurotransmission. SPS exists on a spectrum, with both classical and paraneoplastic variants, the latter often linked to malignancies such as breast cancer.

Methods: This review synthesizes current literature on the pathophysiology, clinical presentation, diagnostic criteria, and treatment modalities of SPS. We examine emerging therapies, including immunomodulatory approaches and antibody-targeted interventions, to address the heterogeneity of disease progression and treatment response.

Results: SPS remains …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

Excess Fructose In High-Fructose Corn Syrup Reduces Cell Viability & Promotes Nitric Oxide Release In Raw 264.7 Macrophages, Renzo F. Galarza, Edward L. Villegas

Research and Creativity Symposium

High-fructose corn syrup (HFCS) is an artificial sweetener that contains slightly higher concentrations of fructose compared to standard sucrose. It has been linked to an increased risk of obesity, type 2 diabetes, cardiovascular disease, and fatty liver disease. While both HFCS and sucrose are widely used sweeteners, growing evidence suggests they may differ in their inflammatory potential. We sought to understand the effects of elevated fructose on RAW 264.7 macrophages. To investigate these effects, we treated the cells with either a sucrose solution or a
solution designed to mimic high-fructose corn syrup. Lipopolysaccharide (LPS) stimulation was used to model innate …

Natural Killer T Cell-Mediated Control Of Francisella Tularensis-Induced Cytokine Storm Syndrome, Cameron M. Torres

Open Access Theses & Dissertations

Inflammation is critical for the effective clearance of viral and bacterial challenges, while simultaneously a mechanism utilized by many highly infectious pathogens to cause disease. The bacterium Francisella tularensis, the causative agent of human tularemia, elicits a cytokine storm, wherein the immune system over-responds to the presence of the bacterium causing a dysregulated release of proinflammatory and regulatory cytokines. Without treatment, tularemia mortality can be as high as 30%, with inhalation of as few as 10 CFUs inducing respiratory tularemia. Natural Killer T (NKT) cells are innate-like T lymphocytes with a diverse array of regulatory functions. Unlike conventional T cells, …

Ai Model For Predicting Asthma Prognosis In Children, Elham Sagheb, Chung-Il Wi, Katherine S King, Bhavani Singh Agnikula Kshatriya, Euijung Ryu, Hongfang Liu, Miguel A Park, Hee Yun Seol, Shauna M Overgaard, Deepak K Sharma, Young J Juhn, Sunghwan Sohn

Faculty, Staff and Student Publications

BACKGROUND: Childhood asthma often continues into adulthood, but some children experience remission. Utilizing electronic health records (EHRs) to predict asthma prognosis can aid health care providers and patients in developing effective prioritized care plans.

OBJECTIVE: We aimed to develop artificial intelligence (AI) models using various clinical variables extracted from EHRs to predict childhood asthma prognosis (remission vs no remission) in different age groups.

METHODS: We developed AI models utilizing patients' EHRs during the first 6, 9, or 12 years of their lives to predict their asthma prognosis status at ages 6 to 9, 9 to 12, or 12 to 15 …

Association Of Delayed Asthma Diagnosis With Asthma Exacerbations In Children, Chung-Il Wi, Euijung Ryu, Katherine S King, Jung Hyun Kwon, Joshua T Bublitz, Miguel Park, Sergio E Chiarella, Jason D Greenwood, Thanai Pongdee, Lynnea Myers, Björn Nordlund, Sunghwan Sohn, Elham Sagheb, Bhavani Singh Agnikula Kshatriya, Dave Watson, Hongfang Liu, Beverley J Sheares, Carla M Davis, Wade Schulz, Young J Juhn

Faculty, Staff and Student Publications

Background: There is a significant delay between symptom onset and diagnosis of childhood asthma, but the impact of this delay on asthma outcomes has not been well understood.

Objectives: We sought to study the association of delayed diagnosis of asthma with asthma exacerbations (AEs) in children.

Methods: Using the Mayo Clinic birth cohort, we identified children with a diagnosis of asthma from electronic health records. We defined onset date as the date when subjects first met predetermined asthma criteria ascertained by an electronic health records-based natural language processing algorithm. Delay in diagnosis (DD) was defined as first diagnosis >30 days …

Immune Landscape Of Early Liver Metastatic Lesions In A Novel Immunocompetent Murine Colorectal Cancer Metastasis Model, Alaa Mohamed

Dissertations and Theses (Open Access)

Colorectal cancer minimal residual disease (MRD) represents a major clinical problem for colorectal cancer patients, with failure rates of surgery and adjuvant chemotherapy between 5% to 40% depending on stage of disease. In our study, we simulated MRD using genetically engineered organoids with precise somatic editing of APC and TP53, creating a murine model that mimics human liver metastatic colorectal cancer. By implementing a meticulously timed experimental metastatic model, we could detect microscopic tumor lesions. Through genomic and transcriptomic analyses, we pinpointed the importance of macrophages, particularly those expressing high levels of CSF1R, in these microscopic metastatic focal lesions. We …

An Investigation Into The Potential Of Cell Therapies For Acute Myeloid Leukemia (Aml) Treatment, Amanda Eckstrom

Dissertations and Theses (Open Access)

Despite recent advances in acute myeloid leukemia (AML) treatment, curative rates remain poor with high rates of relapse and many patients are unable to tolerate the intensive chemotherapy standard of care regimen. Cell therapies have shown great success against hematologic malignancies but face several challenges including treatment-related toxicities and human-leukocyte antigen (HLA) matching. Natural killer (NK) cells and gamma delta (γδ) T cells offer alternative effector cell options for cell therapies that do not require HLA-matching and have shown low toxicity in previous studies. In this project, we sought to evaluate FT538 induced pluripotent stem cell-derived NK (iPSC-NK) and donor-derived …

Intratumoral Fibrin As A Novel Immunomodulatory Factor In Pancreatic Ductal Adenocarcinoma, Mazharul Karim

Open Access Theses & Dissertations

In-situ coagulation is a common clinical feature of pancreatic ductal adenocarcinoma (PDAC) that presents a highly thrombotic and crosslinked insoluble fibrin (x-fibrin)-laden tumor stroma (FibTS). However, the specific impact of FibTS on immune cells behavior remains largely unexplored in this poorly infiltrated tumor. We aimed to elucidate how FibTS in PDAC regulates immune cell infiltration, polarization, and crosstalk that favors immunosuppressive microenvironment and tumor growth. We characterized human PDAC tissues by multiplex immunostaining and checked the spatial distribution of immune cells based on the presence of x-fibrin. We investigated how FibTS influences the infiltration of tumor-associated macrophage (TAM) and T-cell …

Ccr7 Regulated Mechanisms That Limit The Adaptive Immune Response, Jaisel Amilcar Cervantes

Open Access Theses & Dissertations

C-C chemokine receptor 7 (CCR7) is critical in guiding T cell migration within the thymus and peripheral lymphoid tissues, shaping the adaptive immune response by promoting central tolerance and regulating immune homeostasis. Although its role in lymphocyte trafficking is well established, the molecular mechanisms by which CCR7 influences thymocyte development and T cell receptor (TCR) repertoire formation remain less understood. This study examines how CCR7 deficiency impacts thymic selection, TCR diversity, and the signaling events that shape repertoire restriction. Using a homozygously deleted CCR7 murine model, we found that the absence of CCR7 results in a less restricted TCR repertoire …

Short-Course Subcutaneous Alemtuzumab Induces Clinical Responses In Relapsed T-Cell Large Granular Leukemia, Miguel Ruiz, Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Pierluigi Porcu, Jonathan E. Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.

Identification And Catalog Of Viral Transcriptional Regulators In Human Diseases, Citu Citu, Le Chang, Astrid M Manuel, Nitesh Enduru, Zhongming Zhao

Faculty, Staff and Student Publications

Viral genomes encode viral transcriptional regulators (vTRs) that manipulate host gene expression to facilitate replication and evade immune detection. Nevertheless, their role in non-cancerous diseases remains largely underexplored. Here, we unveiled 268 new candidate vTRs from 14 of the 20 viral families we investigated. We mapped vTRs' genome-wide binding profiles and identified their potential human targets, which were enriched in immune-mediated pathways, neurodegenerative disorders, and cancers. Through vTR DNA-binding preference analysis, 283 virus-specific and human-like motifs were identified. Prioritized Epstein-Barr virus (EBV) vTR target genes were associated with multiple sclerosis (MS), rheumatoid arthritis, and systemic lupus erythematosus. The partitioned heritability …

Development Of A Multi-Epitope Peptide Vaccine Against Monkeypox Virus: Immunoinformatics Analysis For South East Asian Hla Alleles, Nelson Chandra, Mochammad Aqilah Herdiansyah, Viol Dhea Kharisma, Arif Nur Muhammad Ansori, Arli Aditya Parikesit

Makara Journal of Science

The monkeypox virus (MPXV), a DNA virus causing zoonotic disease, poses major global public health challenges, with mortality rates between 3%–6%. Although smallpox vaccines provide partial cross-protection, there is a critical need for a dedicated, effective monkeypox (mpox) vaccine. This study aimed to design a multi-epitope peptide-based vaccine specifically adapted to the HLA allele profiles common in Southeast Asian populations, where MPXV cases are rising. Using immunoinformatics, we screened for and detected B and T cell epitopes from the MPXV cell surface antigen and IFN-alpha/beta receptor proteins. The vaccine design was validated through a rigorous evaluation of its antigenicity, immunogenicity, …

An Endocrine Enigma: The Implications Of Pembrolizumab Therapy, Miguel A. Lopez, Mario Trujillo Acosta, Jose Romero Villarreal Calderon, Laura Garcia

Research Symposium

Disorders of the endocrine system are a potential complication of cancer treatment despite newer immunotherapy agents holding promise to improve patient outcomes. Breast cancer in particular requires pharmacologic intervention based on the receptor positivity. For example, a triple negative workup often requires neoadjuvant therapy with the newer immunotherapy agent pembrolizumab. Clinicians should be aware of the potential adverse effects of this drug, most notably adrenal insufficiency. This case follows a 52 year old hispanic female patient with a history of triple negative left sided breast cancer on immunotherapy with pembrolizumab, who presented to the emergency department after a syncopal episode …

Progressive Multifocal Leukoencephalopathy (Pml) Induced By Jc Virus: A Case Report And Review Of Clinical Implications, Hugo Zamarron, Roberto Cruz

Research Symposium

Background: Progressive multifocal leukoencephalopathy (PML) is a rare but serious demyelinating disease of the central nervous system, caused by the John Cunningham (JC) virus. While the JC virus is common in the general population, it remains dormant in healthy individuals but can reactivate in immunocompromised patients, particularly those with HIV/AIDS or undergoing immunosuppressive treatments for organ transplants or autoimmune conditions. The virus attacks oligodendrocytes, leading to demyelination and significant neurological deficits. Immunosuppressive therapies such as natalizumab, rituximab, and mycophenolate increase the risk of PML. Diagnosing PML is challenging as its symptoms—focal neurological deficits, sensory-motor issues, and visual disturbances—overlap with conditions …

Exploring The Mechanisms Of Varicella-Zoster Virus Pathogenesis And Its Potential Role In Oncogenesis, Fernando Cisneros, Blake Martin

Research Symposium

Background: Varicella-zoster virus (VZV) is a highly prevalent pathogen primarily recognized for causing chickenpox during primary infection and herpes zoster (HZ), also known as shingles, upon reactivation. While post-infectious complications of VZV, such as encephalitis, pneumonia, and post-herpetic neuralgia, are well-established, recent large population-based studies suggest that HZ may increase the risk of occult cancers. Emerging evidence suggests that VZV may modulate key oncogenic pathways, such as the inhibition of apoptosis, alteration of cell cycle regulatory enzymes, and interference with immunosurveillance, which could potentially promote cancer development. These findings indicate that VZV’s role in cancer biology may involve direct cellular …

Systems Neuroimmunology: Current Bottlenecks, Research Priorities And Future Directions, Harini Iyer, Christophe Benoist, Staci D Bilbo, Lisa M Boulanger, Michael D Burton, Brian P Daniels, Aleksandra Deczkowska, Martin F Flajnik, Mélanie G Gareau, Peter M Grace, Javier E Irazoqui, Susanna Rosi, Irene Salinas, Anne Schaefer, Caroline L Sokol, Dionna W Williams, Robyn S Klein

Faculty, Staff and Student Publications

Strategies to advance the field of neuroimmunology by embracing its complexity via inclusion of its multidisciplinary properties were discussed at a meeting in Cold Spring Harbor. Attendees proposed fostering of open communications and funding of collaborations across disciplines, and the recognition that our understanding of the neuroimmune system requires interdisciplinary science.

Zika Virus Ns1 Drives Tunneling Nanotube Formation For Mitochondrial Transfer And Stealth Transmission In Trophoblasts, Rafael T Michita, Long B Tran, Steven J Bark, Deepak Kumar, Shay A Toner, Joyce Jose, Indira U Mysorekar, Anoop Narayanan

Faculty, Staff and Students Publications

Zika virus (ZIKV) is unique among orthoflaviviruses in its vertical transmission capacity in humans, yet the underlying mechanisms remain incompletely understood. Here, we show that ZIKV induces tunneling nanotubes (TNTs) in placental trophoblasts which facilitate transfer of viral particles, proteins, mitochondria, and RNA to neighboring uninfected cells. TNT formation is driven exclusively via ZIKV non-structural protein 1 (NS1). Specifically, the N-terminal 1-50 amino acids of membrane-bound ZIKV NS1 are necessary for triggering TNT formation in host cells. Trophoblasts infected with TNT-deficient ZIKV

Mage-A4 Induces Non-Small Cell Lung Cancer And Tumor-Promoting Plasma Cell Accumulation, Dominique Armstrong, Cheng-Yen Chang, Monica J Hong, Linda Green, Yichao Shen, William Hudson, Kelsey E Mauk, Li-Zhen Song, Sheetal Jammi, Benjamin Casal, Brianna Burns, Chad J Creighton, Alexandre Carisey, Xiang H-F Zhang, Neil J Mckenna, Sung Wook Kang, Hyun-Sung Lee, William Decker, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, is expressed in solid tumors and correlates with poor survival, but its role in tumorigenesis and antitumor immunity remains unclear. We found that expression of MAGE-A4 was highly associated with the loss of PTEN, a tumor suppressor, in human non–small cell lung cancers (NSCLC). Here, we show that constitutive expression of human MAGE-A4 with Pten loss in mouse airway epithelia results in metastatic adenocarcinoma. Tumors showed distinct enrichment in IgA+ CD138+ CXCR4+ plasma cells (PCs) and increased expression of …

Evaluating The Impact Of Osteopathic Manipulative Medicine On Cytokine Modulation: A Pathway To Inflammatory Disease Management, Renee M. Chang, Krystal Robinson, Sharon Sengphanith, Grace Godffrey, Jacob Gofrey, Carissa Salamatin, Mark Santos Phd, Wesley Lockhart Do

Annual Research Symposium

No abstract provided.