Background And Purpose: Quantitative T1 mapping can be an essential tool for assessing tissue injury in multiple sclerosis (MS). We introduce T1-REQUIRE, a method that converts a single high-resolution anatomical 3D T1-weighted Turbo Field Echo (3DT1TFE) scan into a parametric T1 map that could be used for quantitative assessment of tissue damage. We present the accuracy and feasibility of this method in MS.
View Article and Find Full Text PDFThe extraction of patient signs and symptoms recorded as free text in electronic health records is critical for precision medicine. Once extracted, signs and symptoms can be made computable by mapping to signs and symptoms in an ontology. Extracting signs and symptoms from free text is tedious and time-consuming.
View Article and Find Full Text PDFBackground: Anti-CD20 is a highly effective therapy for multiple sclerosis (MS), a disease with multiple abnormalities in function of B and T cells and innate immune cells. Anti-CD20 therapy depletes B cells, which alters antibody production and has diverse effects on B cell immunity. These changes potentially affect immunity beyond B cells in MS.
View Article and Find Full Text PDFInterferon (IFN)-β-1a (Avonex) and longer half-life, polyethylene glycol-conjugated IFN-β-1a (PEG-IFN-β-1a, Plegridy), may generate different molecular responses. We identified different short-term and long-term global RNA signatures of IFN-stimulated genes in multiple sclerosis (MS) peripheral blood mononuclear cells and in selected paired serum immune proteins. At 6 h, non-PEGylated IFN-β-1a injection upregulated expression of 136 genes and PEG-IFN-β-1a upregulated 85.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
March 2023
Background And Objectives: Fingolimod, an oral therapy for MS, decreases expression of membrane S1P1 receptors on CD4 memory cells, causing their retention and deactivation in lymph nodes. We determined fingolimod effects on the number and proportion of potentially CNS-damaging CD8CD28 cytolytic T lymphocyte cells (CTLs) and on MS-depleted and dysfunctional CD8CD28 anti-inflammatory suppressor/regulatory T cells (Treg) and on CD8 T-cell expression of the CD69 activation/lymph node retention protein in MS.
Methods: CD8, CD28, CD4, and CD69 expression on peripheral blood mononuclear cells was measured with flow cytometry.
Objective: To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients.
Methods: 30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry.
Bile acids bind to multiple receptors, including Takeda G protein-coupled receptor 5 (TGR5) and farnesoid-X-receptors alpha (FXRα). We compared the response of PBMCs to the activation of these receptors in healthy controls and myasthenic patients. We found that TGR5 is a more potent negative regulator of T cell cytokine response than FXRα in both groups.
View Article and Find Full Text PDFObjective: To determine the effect of vitamin D3 on interferon-β (IFN-β) response and immune regulation in MS mononuclear cells (MNCs).
Methods: MNCs from 126 subjects, including therapy-naive patients with different forms of MS, plus patients with MS receiving IFN-β or glatiramer treatment, plus healthy controls were incubated in vitro with IFN-β-1b ± vitamin D3 (calcitriol). Activation of the IFN-β-induced transcription factor, p-Y-STAT1, and antiviral myxovirus A (MxA) protein was measured with flow cytometry and Western blots; serum proteins were measured with a customized 31-protein multiplex assay.