Cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(11), P. 1990 - 2001

Published: Sept. 14, 2021

SARS-CoV-2 messenger RNA vaccination in healthy individuals generates immune protection against COVID-19. However, little is known about mRNA vaccine-induced responses immunosuppressed patients. We investigated induction of antigen-specific antibody, B cell and T longitudinally patients with multiple sclerosis (MS) on anti-CD20 antibody monotherapy (n = 20) compared controls 10) after BNT162b2 or mRNA-1273 vaccination. Treatment monoclonal (aCD20) significantly reduced spike-specific receptor-binding domain (RBD)-specific memory most patients, an effect ameliorated longer duration from last aCD20 treatment extent reconstitution. By contrast, all MS treated generated CD4 CD8 skewed responses, compromising circulating follicular helper (TFH) augmenting induction, while preserving type 1 (TH1) priming. Patients lacking anti-RBD IgG had the severe defect TFH more robust responses. These data define nature landscape aCD20-treated provide insights into coordinated humans. Our findings have implications for clinical decision-making public health policy including those aCD20.

Language: Английский

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T cells in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

T cells are crucial for immune functions to maintain health and prevent disease. cell development occurs in a stepwise process the thymus mainly generates CD4

Language: Английский

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CAR T therapy beyond cancer: the evolution of a living drug

Nature, Journal Year: 2023, Volume and Issue: 619(7971), P. 707 - 715

Published: July 26, 2023

Language: Английский

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RNA modifications: importance in immune cell biology and related diseases

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Sept. 22, 2022

RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.

Language: Английский

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Metabolic adaptation of lymphocytes in immunity and disease

Immunity, Journal Year: 2022, Volume and Issue: 55(1), P. 14 - 30

Published: Jan. 1, 2022

Adaptive immune responses mediated by T cells and B are crucial for protective immunity against pathogens tumors. Differentiation function of require dynamic reprogramming cellular metabolism. Metabolic inputs, pathways, enzymes display remarkable flexibility heterogeneity, especially in vivo. How metabolic plasticity adaptation dictate functional specialization is fundamental to our understanding therapeutic modulation the system. Extensive progress has been made characterizing effects networks on cell fate discrete microenvironments or immunological contexts. In this review, we summarize how rewiring metabolism determines outcome adaptive vivo, with a focus metabolites, nutrients, driver genes immunometabolism instruct programming during infection, inflammation, cancer mice humans. Understanding context-dependent remodeling will manifest legitimate opportunities intervention human disease.

Language: Английский

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Multiple sclerosis: Neuroimmune crosstalk and therapeutic targeting

Cell, Journal Year: 2023, Volume and Issue: 186(7), P. 1309 - 1327

Published: March 1, 2023

Language: Английский

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Targeted Immunotherapy for Autoimmune Disease

Immune Network, Journal Year: 2022, Volume and Issue: 22(1)

Published: Jan. 1, 2022

In the past few decades, biological drugs and small molecule inhibitors targeting inflammatory cytokines, immune cells, intracellular kinases have become standard-of-care to treat autoimmune diseases. Inhibition of TNF, IL-6, IL-17, IL-23 has revolutionized treatment diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriasis. B cell depletion therapy using anti-CD20 mAbs shown promising results in patients with neuroinflammatory inhibition survival factors is approved for systemic lupus erythematosus. Targeting co-stimulatory molecules expressed on Ag-presenting cells T also expected therapeutic potential diseases by modulating function. Recently, kinase JAK family, which responsible signal transduction from multiple receptors, garnered great interest field hematologic However, there are still unmet medical needs terms efficacy safety profiles. Emerging therapies aim induce tolerance without compromising function, advanced molecular engineering techniques.

Language: Английский

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Age-associated B cells in autoimmune diseases

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(8)

Published: July 7, 2022

Language: Английский

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Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis

JAMA Neurology, Journal Year: 2022, Volume and Issue: 79(11), P. 1105 - 1105

Published: Sept. 19, 2022

Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease unknown.To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard care MG.This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics Sweden. Key inclusion criteria were age older than 18 years, onset symptoms within 12 months or less, Quantitative Myasthenia Gravis (QMG) score 6 more. Patients screened from October 20, 2016, March 2, 2020. exclusion included pure ocular MG, suspected thymoma, previous thymectomy, prior noncorticosteroid immunosuppressants high doses corticosteroids.Participants randomized 1:1 without stratification single intravenous infusion 500 mg matching placebo.Minimal manifestations 16 defined QMG 4 less prednisolone, 10 daily, no rescue treatment.Of 87 potentially eligible patients, 25 (mean [SD] age, 67.4 [13.4] years; [28%] female) 22 58 [18.6] [32%] female). Compared placebo, greater proportion met primary end point; 71% (17 24) group vs 29% (6 21) (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary points, comparing changes Activities Daily Living Quality Life 24 did not differ between groups censoring treatment (per-protocol analysis) favor active when was taken into account by worst rank imputation (post hoc analysis). Rescue treatments also more frequent arm (rituximab: 1 [4%]; 8 [36%]). One patient had myocardial infarction cardiac arrest experienced fatal event.A dose associated minimal MG reduced need medications placebo. Further studies are needed address long-term benefit-risk balance this treatment.ClinicalTrials.gov Identifier: NCT02950155.

Language: Английский

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Xist ribonucleoproteins promote female sex-biased autoimmunity

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 733 - 749.e16

Published: Feb. 1, 2024

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) expressed only in randomly inactivate one of the two X chromosomes achieve gene dosage compensation. Here, we show that ribonucleoprotein (RNP) complex comprising numerous autoantigenic components an important driver sex-biased Inducible transgenic expression a non-silencing form male mice introduced RNP complexes and sufficed produce autoantibodies. Male SJL/J expressing developed severe multi-organ pathology pristane-induced lupus model wild-type males reprogrammed T B cell populations chromatin states resemble females. Human patients autoimmune displayed significant autoantibodies multiple XIST RNP. Thus, sex-specific lncRNA scaffolds ubiquitous drive immunity.

Language: Английский

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