Immune System Diseases Commons^™

Recurrent Miller Fisher Syndrome: A Case Report, Larry Vernier, Griffin B. Gilmore, Kelsey Van Housen, Xiao C. Zhang

Department of Emergency Medicine Faculty Papers

INTRODUCTION: Guillain-Barré syndrome can manifest with progressive paralysis, requiring careful monitoring and treatment with steroids or intravenous (IV) immunoglobin. While this disease can be devastating and require intensive care unit level of care, there are few incidences of relapses.

CASE REPORT: A 67-year-old man with a past medical history of Miller Fisher syndrome variant of Guillain-Barré syndrome, with complete recovery, presented to the emergency department (ED) with ataxia, ophthalmoplegia, dysphonia, and ambulatory dysfunction. The patient noticed his neurologic symptoms after waking up, and he presented to the ED with physical examination positive for difficulty with upward gaze, mild right lower …

The Impact Of Extramedullary And Paraskeletal Plasmacytomas On Treatment Outcomes In Multiple Myeloma Treated With Teclistamab: U.S. Myeloma Immunotherapy Consortium Real-World Experience, Aimaz Afrough, Danai Dima, Beatrice Razzo, Utkarsh Goel, Aishwarya Sannareddy, Oren Pasvolsky, Mariola Vazquez-Martinez, Christopher Ferreri, Rahul Banerjee, Jack Khouri, James Davis, Mahmoud Gaballa, Alex Lieberman-Cribbin, Masooma Rana, Kelley Julian, Faiz Anwer, Leyla Shune, Shaun Dejarnette, Ariel Grajales-Cruz, Evguenia Ouchveridze, Gabriel De Avila, Sandra Susanibar-Adaniya, Andrew Portuguese, Daniel Schrum, Erin Eberwein, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Joseph Mcguirk, Adriana Rossi, Megan Herr, Omar Castaneda, Frederick Locke, Shahzad Raza, Yi Lin, Shebli Atrash, Douglas Sborov, Peter Voorhees, Shambavi Richard, Alfred Garfall, Surbhi Sidana, Krina Patel, Doris Hansen, Andrew Cowan, Larry Anderson, Hans Lee

Department of Medical Oncology Faculty Papers

Teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA), is effective in relapsed or refractory multiple myeloma (RRMM), but its impact on patients with soft tissue plasmacytomas is unclear. We studied 385 RRMM patients treated with teclistamab at 13 U.S. centers through September 2023, with follow-up to April 2024. Soft tissue plasmacytomas were classified as true extramedullary disease (EMD; not contiguous with bone) or paraskeletal plasmacytomas (PSK; contiguous with bone). Patients with the simultaneous presence of both were classified as true-EMD, reflecting its adverse prognosis. Of those, 109 (28%) had true EMD, 33 (9%) had PSK, and 243 (63%) had …

Promising Effects Of Car T-Cell Therapy In Refractory Stiff Person Syndrome And A Hopeful Future For All Neuroautoimmunities, Marinos Dalakas

Department of Neurology Faculty Papers

Chimeric antigen receptor (CAR) T cells are genetically modified T cells expressing CARs, initially developed to recognize tumor antigens and kill cancer cells that evade T-cell recognition. Because of their impressive success in hemato-oncologic malignancies, CAR T cells are being repurposed with redesigned constructs for safety and sustained efficacy to target refractory systemic autoimmune or neurologic diseases. The CD19 CAR T cells-targeting those CD19-positive, antibody-secreting, long-lived plasma cells, and plasmablasts-are now extensively explored in refractory neuroautoimmunities with promising benefits based on case series in patients with myasthenia gravis (MG), stiff person syndrome (SPS), neuromyelitis, myositis, and multiple sclerosis; some patients …

Editorial: Women In Science: Allergy Research, Gemma Carreras-Badosa, Vanesa Esteban, Vivian Hernandez-Trujillo, Elina Toskala, Manali Mukherjee, Saba Al Heialy, Karin Fieten

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

No abstract provided.

Use Of Upadacitinib For Recalcitrant Oral Erosive Lichen Planus, Connor A. Sheehan, Nicholas D. Brownstone, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Prevalence Of Autoimmune Diseases In Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network Of Health Care Organizations, Pushti Khandwala, Devashish Desai, Arthur Lau

Einstein Health Papers

OBJECTIVE: Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement of immune checkpoint inhibitors (ICIs).

METHODS: This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved were stratified into two groups based on ICI use. Multivariate Cox proportional hazard models and Kaplan Meier method were used to assess risk of developing ACs among the groups. Subgroup analysis was done to evaluate risk of ACs in patients receiving cytotoxic T-lymphocyte-associated protein 4 inhibitor (CTLA4i) versus program cell death protein 1 inhibitor (PD1i) and program death ligand 1 inhibitor (PDL1i) inhibitors and combination treatment (CT) …

Atrial Fibrillation Recurrence Risk After Catheter Ablation In Patients With Rheumatoid Arthritis: A Systematic Review And Meta-Analysis, Pongprueth Rujirachun, Phuuwadith Wattanachayakul, Svita Taveeamornrat, Patompong Ungprasert, Nithi Tokavanich, Krit Jongnarangsin

Einstein Health Papers

BACKGROUND: The association between rheumatoid arthritis (RA) and the risk of developing atrial fibrillation (AF) is well-established. However, data on the impact of RA on AF recurrence postcatheter ablation (CA) remain unclear. This current study aimed to assess the impact of RA on AF recurrence after catheter-based pulmonary vein isolation.

METHODS: Potentially eligible studies were identified from Medline and EMBASE databases from inception to December 20, 2023. Eligible study must consist of two cohorts of patients with and without RA who underwent catheter ablation for AF. Pooled risk ratio (RR) and 95% CI were calculated using Dersimonian and Laird's random-effect, …

The Impact Of Telemedicine On Human Immunodeficiency Virus (Hiv)-Related Clinical Outcomes During The Covid-19 Pandemic, Avery Lin Cox, Daniel Tsang, Lisa A. Spacek, Constantine Daskalakis, Dagan Coppock

Division of Infectious Diseases and Environmental Medicine Faculty Papers

The coronavirus disease of 2019 (COVID-19) pandemic exacerbated barriers to care for people living with human immunodeficiency virus (HIV) (PLWH). The quick uptake of telemedicine in the outpatient setting provided promise for care continuity. In this study, we compared appointment and laboratory no-show rates in an urban outpatient HIV clinic during three time periods: (1) Pre-COVID-19: 9/15/2019-3/14/2020 (predominately in-person), (2) "Early" COVID-19: 3/15/2020-9/14/2020 (predominately telemedicine), and (3) "Later" COVID-19: 9/15/2020-3/14/2021 (mixed in-person/telemedicine). Multivariable logistic regression models evaluated the two study hypotheses: (i) equivalence of Period 2 with Period 1 and of Period 3 with Period 1 and (ii) improved outcomes …

Objectivity, Practicality, And Significance Of Practice Guidelines For The Practicing Neurologists: What We Learnt From Consensus Criteria In Cidp, Myasthenia Gravis And Inflammatory Myopathies, Marinos C. Dalakas

Department of Neurology Faculty Papers

The value of practice guidelines in the three most common autoimmune neuromuscular disorders, namely Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), Myasthenia Gravis (MG) and Autoimmune Inflammatory Myopathies (AIM), has been extensively debated regarding their usefulness in clinical practice, objectivity and universal value considering that guidelines are also established regionally in certain countries. This commentary highlights common concerns on how guidelines are presently generated, pointing out: (a) non-sufficient diversity among Task-Force members to identify and address not only routine clinical and electrophysiology issues but also immunology, imaging, pathology, biomarkers, epidemiology or treatment economics; (b) Task-Force being often comprised by the same or …

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Immune Reconstitution But Persistent Activation After 48 Weeks Of Antiretroviral Therapy In Youth With Pre-Therapy Cd4 >350 In Atn 061., Bret J. Rudy, Bill G. Kapogiannis, Carol Worrell, Kathleen E. Squires, James Bethel, Su Li, Craig M. Wilson, Allison Agwu, Patricia Emmanuel, Georgine Price, Stephanie Hudey, Maureen M. Goodenow, John W. Sleasman

Department of Medicine Faculty Papers

BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited.

DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48.

METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls.

RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, …

Asymmetric Deactivation Of Hiv-1 Gp41 Following Fusion Inhibitor Binding., Kristen M Kahle, H Kirby Steger, Michael J Root

Department of Biochemistry and Molecular Biology Faculty Papers

Both equilibrium and nonequilibrium factors influence the efficacy of pharmaceutical agents that target intermediate states of biochemical reactions. We explored the intermediate state inhibition of gp41, part of the HIV-1 envelope glycoprotein complex (Env) that promotes viral entry through membrane fusion. This process involves a series of gp41 conformational changes coordinated by Env interactions with cellular CD4 and a chemokine receptor. In a kinetic window between CD4 binding and membrane fusion, the N- and C-terminal regions of the gp41 ectodomain become transiently susceptible to inhibitors that disrupt Env structural transitions. In this study, we sought to identify kinetic parameters that …

Combined Effects Of Hyperglycemic Conditions And Hiv-1 Nef: A Potential Model For Induced Hiv Neuropathogenesis., Edward A Acheampong, Cassandra Roschel, Muhammad Mukhtar, Alagarsamy Srinivasan, Mohammad Rafi, Roger J Pomerantz, Zahida Parveen

Department of Neurology Faculty Papers

Hyperglycemic conditions associated with diabetes mellitus (DM) or with the use of antiretroviral therapy may increase the risk of central nervous system (CNS) disorders in HIV-1 infected patients. In support of this hypothesis, we investigated the combined effects of hyperglycemic conditions and HIV-1 accessory protein Nef on the CNS using both in vitro and in vivo models. Astrocytes, the most abundant glial cell type required for normal synaptic transmission and other functions were selected for our in vitro study. The results show that in vitro hyperglycemic conditions enhance the expression of proinflammatory cytokines including caspase-3, complement factor 3 (C3), and …

A Comprehensive Analysis Of The Naturally Occurring Polymorphisms In Hiv-1 Vpr: Potential Impact On Ctl Epitopes., Alagarsamy Srinivasan, Velpandi Ayyavoo, Sundarasamy Mahalingam, Aarthi Kannan, Anne Boyd, Debduti Datta, Vaniambadi S Kalyanaraman, Anthony Cristillo, Ronald G Collman, Nelly Morellet, Bassel E Sawaya, Ramachandran Murali

Department of Microbiology and Immunology Faculty Papers

The enormous genetic variability reported in HIV-1 has posed problems in the treatment of infected individuals. This is evident in the form of HIV-1 resistant to antiviral agents, neutralizing antibodies and cytotoxic T lymphocytes (CTLs) involving multiple viral gene products. Based on this, it has been suggested that a comprehensive analysis of the polymorphisms in HIV proteins is of value for understanding the virus transmission and pathogenesis as well as for the efforts towards developing anti-viral therapeutics and vaccines. This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates …