Self-reported longitudinal COVID-19 vaccination reactogenicity profiles in persons with multiple sclerosis.

Background: Preventing severe COVID-19 associated outcomes continues to be a priority for persons with multiple sclerosis (PwMS). We previously reported in an interim analysis that short-term reactions to the first and second SARS-CoV-2 vaccines experienced by PwMS were mostly self-limiting and similar to reactions experienced by the general population.

Objectives: First, to report short-term reactogenicity experienced by PwMS in relation to the first through fourth SARS-CoV-2 vaccines.

The AlzMatch Pilot Study - Feasibility of Remote Blood Collection of Plasma Biomarkers for Preclinical Alzheimer's Disease Trials.

Background: Advances in plasma biomarkers to detect Alzheimer's disease (AD) biology allows researchers to improve the efficiency of participant recruitment into preclinical trials. Recently, protein levels of plasma amyloid-beta and tau proteins have been shown to be predictive of elevated amyloid in brain. Online registries, such as the Alzheimer's Prevention Trials (APT) Webstudy, include and follow participants using remote assessments to facilitate efficient screening and enrollment of large numbers of individuals who may be at higher risk for AD.

IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4 T cell responses following COVID-19 mRNA vaccination.

Background: The innate immune cytokine interleukin (IL)-1 can affect T cell immunity, a critical factor in host defense. In a previous study, we identified a subset of human CD4 T cells which express IL-1 receptor 1 (IL-1R1). However, the expression of such receptor by viral antigen-specific CD4 T cells and its biological implication remain largely unexplored.

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs.

Clinical utility of plasma Aβ42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aβ42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear.

Methods: Aβ42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aβ42/40 testing.

Results: High diagnostic sensitivity and negative predictive value (NPV) for Aβ-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aβ42/40 values for individuals with positive vs negative Aβ-PET results.

Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination.

BACKGROUNDWhile B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODSWe evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.

Microfluidic Immuno-Serolomic Assay Reveals Systems Level Association with COVID-19 Pathology and Vaccine Protection.

How to develop highly informative serology assays to evaluate the quality of immune protection against coronavirus disease-19 (COVID-19) has been a global pursuit over the past years. Here, a microfluidic high-plex immuno-serolomic assay is developed to simultaneously measure50 plasma or serum samples for50 soluble markers including 35proteins, 11 anti-spike/receptor binding domian (RBD) IgG antibodies spanningmajor variants, and controls. This assay demonstrates the quintuplicate test in a single run with high throughput, low sample volume, high reproducibilityand accuracy.

Recurrent Optic Neuritis and Perineuritis Followed by an Unexpected Discovery: From the National Multiple Sclerosis Society Case Conference Proceedings.

We describe a woman with a history of relapsing acute optic neuritis and perineuritis. Testing failed to confirm a specific diagnosis; hence, she was diagnosed with seronegative neuromyelitis optica spectrum disorder and treated with the immunotherapy rituximab, later in conjunction with mycophenolate mofetil. She achieved a durable remission for 9 years until she presented with paresthesia affecting her left fifth digit, right proximal thigh, and left foot, while also reporting a 25-pound weight loss over the prior 3 months.

Multiple Sclerosis Followed by Neuromyelitis Optica Spectrum Disorder: From the National Multiple Sclerosis Society Case Conference Proceedings.

A woman presented at age 18 years with partial myelitis and diplopia and experienced multiple subsequent relapses. Her MRI demonstrated T2 abnormalities characteristic of multiple sclerosis (MS) (white matter ovoid lesions and Dawson fingers), and CSF demonstrated an elevated IgG index and oligoclonal bands restricted to the CSF. Diagnosed with clinically definite relapsing-remitting MS, she was treated with various MS disease-modifying therapies and eventually began experiencing secondary progression.

Microfluidic immuno-serology assay revealed a limited diversity of protection against COVID-19 in patients with altered immunity.

The immune response to SARS-CoV-2 for patients with altered immunity such as hematologic malignancies and autoimmune disease may differ substantially from that in general population. These patients remain at high risk despite wide-spread adoption of vaccination. It is critical to examine the differences at the systems level between the general population and the patients with altered immunity in terms of immunologic and serological responses to COVID-19 infection and vaccination.

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4 T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs).

Changes in ganglioside antibody positivity rates during the COVID-19 pandemic.

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b.

Pain in Multiple Sclerosis: Understanding Pathophysiology, Diagnosis, and Management Through Clinical Vignettes.

Neuropathic pain and other pain syndromes occur in the vast majority of patients with multiple sclerosis at some time during their disease course. Pain can become chronic and paroxysmal. In this review, we will utilize clinical vignettes to describe various pain syndromes associated with multiple sclerosis and their pathophysiology.

COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis.

Background And Objectives: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.

Methods: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes.

B cell depletion changes the immune cell profile in multiple sclerosis patients: One-year report.

B cell depletion therapy has been shown to be beneficial in multiple sclerosis (MS). However, the mechanism by which B cell depletion mediates its beneficial effects in MS is still unclear. To better understand how B cell depletion may benefit patients with a disease previously thought to be primarily mediated by CD4 T cells, immune profiles were monitored in 48 patients in a phase II trial of ublituximab, a glycoengineered CD20 monoclonal antibody, at 18 time points over a year.

A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg balance.

Reestablishing an appropriate balance between T effector cells (Teff) and Tregs is essential for correcting autoimmunity. Multiple sclerosis (MS) is an immune-mediated chronic CNS disease characterized by neuroinflammation, demyelination, and neuronal degeneration, in which the Teff:Treg balance is skewed toward pathogenic Teffs Th1 and Th17 cells. STAT3 is a key regulator of Teff:Treg balance.

Progressive multifocal leukoencephalopathy in dimethyl fumarate-treated multiple sclerosis patients.

Dimethyl fumarate (DMF), a fumaric acid with antioxidant and immunomodulatory properties, is among the most commonly used oral therapies for relapsing multiple sclerosis (MS). Progressive multifocal leukoencephalopathy (PML) has been associated with several disease-modifying therapies (DMTs), including DMF in treating MS. We present detailed clinical characteristics of nine PML cases and show that the PML incidence in DMF-treated patients is 0.

B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, thought to be mediated by myelin-specific CD4+ T cells. However, B cell depletion has proven to be an effective therapy for MS, but the mechanism is not well understood. This study was designed to determine how B cell depletion changes lymphocyte profiles.

Ocrelizumab infusion experience in patients with relapsing and primary progressive multiple sclerosis: Results from the phase 3 randomized OPERA I, OPERA II, and ORATORIO studies.

Background: Ocrelizumab is an infusible humanized monoclonal antibody that selectively depletes CD20 B cells. Infusion-related reactions (IRRs) were summarized from the OPERA I, OPERA II, and ORATORIO trials for relapsing and primary progressive multiple sclerosis (MS).

Methods: OPERA I and OPERA II were identical, randomized, double-blind, active-controlled trials that enrolled patients with relapsing MS (RMS).

Novel small molecule IL-6 inhibitor suppresses autoreactive Th17 development and promotes T development.

Multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in the United States in young adults, but current treatments are only partially effective, making it necessary to develop new, innovative therapeutic strategies. Myelin-specific interleukin (IL)-17-producing T helper type 17 (Th17) cells are a major subset of CD4 T effector cells (T ) that play a critical role in mediating the development and progression of MS and its mouse model, experimental autoimmune encephalomyelitis (EAE), while regulatory T cells (T ) CD4 T cells are beneficial for suppressing disease. The IL-6/signal transducer and activator of transcription 3 (STAT-3) signaling pathway is a key regulator of Th17 and T cells by promoting Th17 development and suppressing T development.