3-in-one PD-1CAR Tregs: A bioengineered cellular therapy for target engagement, activation, and immunosuppression with reparative potential

iScience · 2025-10-04 · 1 citations

CAR Tregs as a unique therapy with both targeted suppression and tissue repair potential.

255 - Beyond Sensory: SNM Lead Sensing Consistently Measures Patient-Specific Sacral Evoked Responses

Continence · 2024-10-01

Transitioning to e-cigarettes restores the immune response to house dust mites in cigarette smoked mice

bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-06

Abstract Since the introduction of electronic cigarettes to the US market, e-cigarettes have been posited as a safe alternative to combustible cigarettes. We developed a preclinical animal model to determine whether transitioning to e-cigarette use after up to 16 weeks of daily exposure to combustible cigarette smoke (CS) could restore normal lung immune responsiveness to house dust mites (HDM). In these studies, CS exposed animals were randomly assigned to 6 groups. (1) CS-CS mice continued combustible cigarette exposure for an additional 7 or 16 weeks, and (2) CS-recovery mice were removed from cigarette smoking where they recovered without intervention. (3) CS-carrier mice transitioned to vaporized propylene glycol (30%) with vegetable glycerol (70%) (i.e. carrier). (4) CS-salt mice transitioned to e-vapor exposure containing nicotine salt (liquid nicotine in benzoic acid + carrier), and (5) CS-base mice transitioned to daily exposures to liquid nicotine + carrier containing e-vapors. (6) Room air exposed mice, that were not smoked or exposed to e-cigarette vapors, were included as controls. We hypothesized that transitioning from CS to either of the three e-cigarette exposures (base, salt or carrier) would restore eosinophil influx into the airways following intranasal HDM administration. Here we report that shorter (7 week) e-vapor exposure containing salt, base or carrier led to significant eosinophil responses following HDM challenge. In the 16-week model, CS-base and CS-salt exposed animals did not regain their HDM responsiveness when compared to controls. CS-carrier mice did regain partial responses to HDM at 16 weeks as indicated by an increase in eosinophils compared to control mice. Lung resident lymphoid cells support the influx of eosinophils following allergen exposure. As such we measured total T cells, B cells and group 2 innate lymphoid cells (ILC2) in the lungs of each of the treatment groups. ILC2 and CD4+ T cells were reduced, and B cells were increased in the lungs of CS mice compared to controls. Numerically, the transition to nicotine-salt increased the CD3+ T cell response but transitioning to the nicotine-base significantly reduced CD19 B cells. Additional studies showed that GM-CSF protein was increased in cultured ILC and in whole lung tissues of control mice compared to CS-carrier mice indicating plasticity of the ILC2 population. RNA microarray analyses identified significant increases in GM-CSF, CCL17 and CCL24 transcripts in alveolar macrophages following the transition from CS to carrier compared to control mice. In summary, the immunosuppressive effects of CS may be restored following short-term use of e-cigarettes, but chronic use of e-cigarettes may blunt pulmonary immunity similarly to traditional cigarette smoke.

Presymptomatic Aquaporin-4 (AQP4) Autoantibody Seropositivity in NMOSD: Analysis of the Department of Defense Serum Repository (DoDSR) (S50.005)

Neurology · 2023-04-25 · 1 citations

<h3>Objective:</h3> Determine whether antibodies to AQP4 are present in pre-symptomatic serum from patients with neuromyelitis spectrum disorder (NMOSD) in the DoDSR <h3>Background:</h3> NMOSD is an autoimmune disease primarily targeting the spinal cord and optic nerve, leading to paralysis and blindness. Antibodies directed against AQP4 are a key element of disease pathogenesis and provide a disease-specific marker of NMOSD pathology. One small study of patients with myasthenia gravis suggested that antibodies to AQP4 may be present as long as 16 years prior to onset of NMOSD; however, difficulty obtaining pre-symptomatic serum samples for rare diseases has limited our ability to test for the presymptomatic presence of this biomarker. <h3>Design/Methods:</h3> Subjects were identified through the DoD/Defense Medical Surveillance System (DMSS) utilizing ICD codes for Neuromyelitis Optica (ICD-9: 341.0, ICD10: G36.0). After verifying the clinical and laboratory records of each patient to ensure the correct diagnosis, a list of these potential subjects was sent to the Armed Forces Health Surveillance Division (AFHSD) to determine which had serum specimens. Serum from these patients, as well as age and sex-matched healthy and disease (multiple sclerosis) controls, was acquired from the DoDSR at the time closest to diagnosis and at timepoints up to 20 years prior to diagnosis. Serum from these samples was analyzed for AQP4 antibodies using Euroimmun fixed cell-based assays performed at ARUP. <h3>Results:</h3> 64 people who met inclusion criteria were identified and analyzed for autoantibodies to AQP4. Of 32 AQP4-positive patients analyzed for seropositivity in the sample prior to disease onset, 20 (62.5%) were positive for AQP4 (mean −940 days, SD −400.5); analysis of older serum samples will be presented at the conference. <h3>Conclusions:</h3> Antibodies to AQP4 are present in a subset of patients with NMOSD years prior to diagnosis. Additional studies are needed to determine what factors predict onset of disease. <b>Disclosure:</b> Dr. Smith has nothing to disclose. Mr. Wong has nothing to disclose. The institution of Dr. Peterson has received research support from Kronus. The institution of Mr. Carlson has received research support from Biogen. Mr. Carlson has received personal compensation in the range of $100,000-$499,999 for serving as a Employee as a Researcher with Veteran Affairs. The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care. Dr. Horvat has nothing to disclose. Dr. Groshans has nothing to disclose. Dr. Mabila has nothing to disclose. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech, Inc.. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics, Inc.. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Prime Therapeutics. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedImmune/Viela Bio. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Arialys Therapeutics. The institution of Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche/Genentech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB, Inc. Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Hoffman/LaRoche AG. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genetech. Dr. Pittock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for F. Hofman/LaRoche. The institution of Dr. Pittock has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Pittock has received research support from Grifols. The institution of Dr. Pittock has received research support from NIH. The institution of Dr. Pittock has received research support from Viela Bio/MedImmune/Horizon. The institution of Dr. Pittock has received research support from Alexion Pharmaceuticals. The institution of Dr. Pittock has received research support from F. Hoffman/LaRoche/Genentech. The institution of Dr. Pittock has received research support from NovelMed. The institution of Dr. Pittock has received research support from AstaZeneca. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Pittock has received intellectual property interests from a discovery or technology relating to health care. Dr. Tagg has stock in Apple, Birkshire Hathaway, Medtronic. Dr. Clardy has received personal compensation for serving as an employee of Veterans Health Administration (VHA). Dr. Clardy has received personal compensation for serving as an employee of University of Utah Health. Dr. Clardy has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology/AAN Publications. The institution of Dr. Clardy has received research support from Sumaira Foundation for NMO. The institution of Dr. Clardy has received research support from Western Institute for Veteran Research. The institution of Dr. Clardy has received research support from NIH/NINDS. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a AAN Summer Meeting CoDirector Travel and Lodging with AAN. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Grand Rounds Travel and Lodging with U of Iowa. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Barrow Neurological Institute. Dr. Clardy has received personal compensation in the range of $500-$4,999 for serving as a Speaker Honoraria for Grand Rounds with Beaumont Health.

SENSING IN SACRAL NEUROMODULATION: SACRAL EVOKED RESPONSES AS OBJECTIVE, PATIENT-SPECIFIC MEASURES OF STIMULATION PROGRAMS

Continence · 2023-07-13 · 1 citations

Neuronal Uptake of Paraneoplastic and Other IgGs is Mediated by the Fc Portion of the IgG Molecule and Involves Previously Uncharacterized Neuronal FcγRI Receptors: Implications for Antibody-Mediated Neuronal Injury

Neurology · 2022-12-05

ConclusionsMyeloradiculitis has been reported with anti-MOG disease but is not a typical finding for NMO.We report this case to highlight this unusual finding.In addition, sarcoma is an uncommon cause of paraneoplastic syndromes and to our knowledge, this is the first report of sarcoma being associated with paraneoplastic NMOSD.

Quantitative Analysis of MS Lesion in Cervical Spinal Cord (CSC) using Ultrahigh-b DWI (UHb-DWI) (P15-4.006)

Neurology · 2022-05-03

To investigate UHb-rDWI signal in CSC White-matter and compare quantitative values between healthy control WM with both MS NAWM and MS WM lesions.

Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis

Frontiers in Neurology · 2022 · 40 citations

• Immunology
• Medicine
• Biology

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.

Quantitative Analysis of Wild Type (WT) and Shiverer (SHR) Mouse Spinal Cords using Ultrahigh-b DWI (UHb-DWI) (P3-4.010)

Neurology · 2022-05-03

To perform a quantitative evaluation of myelination on myelin-deficient (shiverer) and WT mouse spinal cords using UHb-DWI.

Interaction of Anti-Yo and anti-Hu Antibodies with Neurons in Living Mice Following Intracranial Injection or Infusion: Demonstration of Neuronal Antibody Uptake and Early Detection of Neuronal Death (S41.004)

Neurology · 2022-05-03

1) To determine whether anti-Yo and anti-Hu antibodies are taken up by neurons and cause neuronal death in living animals, as has been shown to occur in rodent brain slice cultures. 2) To determine whether methods of detecting neuronal death in slice culture can be used to study brains of animals following antibody infusion.