B-cell depletion in autoimmune diseases

Annals of the Rheumatic Diseases, Journal Year: 2024, Volume and Issue: unknown, P. ard - 225727

Published: May 22, 2024

B cells have a pivotal function in the pathogenesis of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. In disease, orchestrate antigen presentation, cytokine production autoantibody production, latter via their differentiation into antibody-secreting plasmablasts plasma cells. This article addresses current therapeutic strategies to deplete order ameliorate or potentially even cure disease. It main target antigens B-cell lineage that are used for approaches. Furthermore, it summarises evidence successful treatment disease with monoclonal antibodies targeting limitations challenges these Finally, concept deep depletion immunological reset by chimeric receptor T is discussed, well lessons from this approach better understanding role

Language: Английский

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Early immune factors associated with the development of post-acute sequelae of SARS-CoV-2 infection in hospitalized and non-hospitalized individuals

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 22, 2024

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that persist for weeks years following initial viral infection. Clinical manifestations PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms its associated symptoms, biological drivers still unknown. We enrolled 494 patients with COVID-19 at their presentation a hospital or clinic followed them longitudinally determine development PASC. From 341 patients, we conducted multi-omic profiling peripheral blood samples collected shortly after study enrollment investigate early immune signatures During first week COVID-19, observed large number differences in profile individuals who were hospitalized compared those not hospitalized. Differences between did later develop were, comparison, more limited, but included significant autoantibodies epigenetic transcriptional double-negative 1 B cells, particular. found indicators incident nuanced, molecular signals manifesting predominantly robust hospitalization during COVID-19. The emerging cell phenotypes, especially highlight potentially important role these cells

Language: Английский

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Adaptive immunity and atherosclerosis: aging at its crossroads

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 15, 2024

Adaptive immunity plays a profound role in atherosclerosis pathogenesis by regulating antigen-specific responses, inflammatory signaling and antibody production. However, as we age, our immune system undergoes gradual functional decline, phenomenon termed “immunosenescence”. This decline is characterized reduction proliferative naïve B- T cells, decreased cell receptor repertoire pro-inflammatory senescence associated secretory profile. Furthermore, aging affects germinal center responses deteriorates secondary lymphoid organ function structure, leading to impaired T-B dynamics increased autoantibody In this review, will dissect the impact of on adaptive played age-associated cells pathogenesis, emphasizing need for interventions that target age-related dysfunction reduce cardiovascular disease risk.

Language: Английский

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In situ engineering of mRNA-CAR T cells using spleen-targeted ionizable lipid nanoparticles to eliminate cancer cells

Nano Today, Journal Year: 2024, Volume and Issue: 59, P. 102518 - 102518

Published: Oct. 3, 2024

Language: Английский

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A cost-effective approach for comprehensive analysis of human memory B Cell repertoire: fast isolation of broad neutralizing mAbs to SARS-CoV-2 variants

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Abstract The SARS-CoV-2 pandemic highlighted the urgent need for innovative methods to study humoral immune responses and identify monoclonal antibodies (mAbs) with diagnostic therapeutic potential. Memory B cells (MBCs), pivotal adaptive immunity, generate high-affinity upon antigen re-encounter. While single-cell high-throughput sequencing has revolutionized antibody repertoire studies, it critical limitations: inability simultaneously determine antigen-binding specificities immunoglobulin gene sequences, high resource demands that limit accessibility in low-resource settings. Here, we present a cost-effective culture (SCC) platform enabling comprehensive analysis of human MBC repertoires, including epitope-specific responses, cross-reactivity mAb isolation. Using convalescent vaccinated donor samples, optimized SCCs NB21 feeder cells, R848, IL-2 stimulation, achieving cloning efficiency 30-fold enrichment antigen-specific MBCs compared bulk cultures. Among 592 isolated mAbs, 52.7% exhibited specificity Wuhan strain Spike protein, 27.9% targeting receptor-binding domain (RBD), 15.4% N-terminal (NTD), 56.7% other regions, likely S2 domain. Comparative revealed distinct patterns: 40.5% all anti-Spike mAbs recognized tested variants (Wuhan, Beta, Delta, Gamma Omicron BA.2), while 29.6% showed recognition only four variants, majority not BA.2; 56 single reactive (14.9%) were also identified. Notably, screening neutralization assays performed directly supernatants, eliminating large-scale transfection. Desired clones selected recombinant production. SCC enabled unbiased profiling, revealing convergent V-region rearrangements, public V3-30 V3-53/V3-66 consistent prior studies. Two RBD-targeting broad potential validated pseudovirus assays. This streamlined delivers simultaneous isolation, sequencing, functional studies within seven days, empowering researchers settings address global health inequities enhance preparedness future pandemics.

Language: Английский

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Unraveling Novel Subsets of Lymphocytes Involved in Sac Expansion in the Tertiary Lymphoid Structure Within an Abdominal Aortic Aneurysm

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

Background Chronic inflammation is involved in the development of abdominal aortic aneurysm (AAA). A tertiary lymphoid structure (TLS) within vascular lesions has recently been focused on for its role modulation local tissues. We aimed to elucidate relationships between TLS and pathophysiology AAA. Methods Abdominal samples obtained from 37 patients with AAA (men/women: 34/3, age: 72.8±9.9 years) 15 autopsied who died non‐aortic events 11/4, 65.5±9.8 were investigated. Results TLSs confirmed by focal infiltration CD3‐positive cells surrounding germinal center‐like structures containing CD20‐positive tunica adventitia media layers. The formation a was significantly more prevalent than patients. number positively correlated sac diameter (r=0.357, P =0.035) amount intraluminal thrombosis (r=0.466, =0.005). T B predominant cellular populations among CD45 + lesions. There positive correlation proportions interfollicular follicular helper (CD3 CD4 CD45RA − CXCR5 PD‐1 ) double negative CD19 IgD CD27 cells, they diameter, thrombosis, serum lipids. Deposited single‐cell RNA‐sequencing data showed that associated lipid metabolism, cell activation/proliferation inflammation. Conclusions connection which may contribute might be novel therapeutic targets

Language: Английский

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Short-term fasting before living kidney donation has an immune-modulatory effect

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

Short-Term Fasting (STF) is an intervention reducing the intake of calories, without causing undernutrition or micronutrient-related malnutrition. It aims to systemically improve resilience against acute stress. Several (pre-)clinical studies have suggested protective effects STF, marking systemic STF can induce in respect surgery and ischemia-reperfusion injury. In addition, also affects number circulating immune cells. We aim determine effect on abundance phenotype different cell populations. Thirty participants were randomly selected from FAST clinical trial, including living kidney donors, randomized STF-diet control arm. observational cohort sub-study we prospectively included 30 patients who donated blood samples repeatedly during study runtime. Using flow cytometry analyses, phenotyping was performed peripheral mononuclear Three panels designed investigate presence activation status T cells, B dendritic cells (DCs) myeloid Eight excluded due sample constraints. Baseline characteristics showed no significant differences, except for fasting duration. Weight changes minimal non-significant across time intervals, with slight trends toward long-term weight loss pre-surgery. Glucose, insulin, β-hydroxybutyrate levels differed significantly between groups, reflecting adherence diet. Flow RNA sequencing analysis revealed baseline differences high variability within each group. regulatory increased (naïve) elevation type 1 conventional DCs (cDC1s). a decrease central memory observed. this study, observed DCs, specifically less specialized lymphocytes, suggesting arrest development. Further research should focus implications significance these immunological changes. results reduced numbers Tregs, cDC1s.

Language: Английский

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Tumor-infiltrating and circulating B cells mediate local and systemic immunomodulatory mechanisms in Glioblastoma

Journal of Neuro-Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

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Treatment strategy for systemic lupus erythematosus using belimumab as indicated by multi‐omics analysis

Rheumatology & autoimmunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 12, 2025

Abstract Belimumab is an antibody targeting the cytokine B‐cell activating factor (BAFF), which crucial for B cell differentiation, and first molecularly targeted drug approved systemic lupus erythematosus (SLE). The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications, as well nephritis. In addition, effects preventing relapses reducing glucocorticoid use confirmed. Moreover, there were no significant differences incidences many adverse events between placebo groups. Recent multi‐omics analyses revealed that cells by are limited to naïve a subset memory cells. These findings align efficacy safety profile belimumab. An improved understanding mechanism action could support its earlier during treatment course or broader range cases.

Language: Английский

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Relationships among immune cells, metabolites, and non-small cell lung cancer: a mediation Mendelian randomization study

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 9, 2025

Language: Английский

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