A unique human cord blood CD8⁺CD45RA⁺CD27⁺CD161⁺T cell subset identified by flow cytometric data analysis using Seurat

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 3, 2023

Abstract Advances in single cell analysis, especially cytometric approaches, have profoundly innovated immunological research. This has resulted an expansion of high dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis thus becomes untenable, while most computational methods lack flexibility interoperability, hampering usability. Here, the first time, we adapted Seurat, a RNA sequencing (scRNA-seq) package, end-to-end flow data We showcased its robust analytical capacity by analyzing adult blood cord T profiles, which was validated Spectre, another Importantly, unique CD8 + CD45RA CD27 CD161 subset, identified characterized using cytometry scRNA-seq from published dataset. Collectively, Seurat possesses potential It facilitates thorough interpretations pipeline, implementing data-driven investigation clinical immunology.

Language: Английский

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Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Journal of Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 154(3), P. 754 - 766.e7

Published: May 17, 2024

Background Despite impaired humoral responses in patients treated with immunosuppressants (ISPs), recent studies found similar severity of SARS-CoV-2 breakthrough infections compared to controls. One potential explanation is the rapid generation upon infection, but evidence lacking. Objectives To investigate longitudinal dynamics antibody repertoire after delta and omicron immune-mediated inflammatory diseases (IMID) on ISPs Methods As prospective sub-study national Target-to-B! (T2B!) consortium, we included IMID controls who reported between July 1, 2021, April 2022. get an impression repertoire, three titers wild-type RBD, S, RBD were measured at four time points infections. Results We 302 178 Antibody increased up 28 days both groups. However, anti-CD20 therapy sphingosine-1 phosphate receptor (S1P) modulators, considerably lower In anti-TNF group, observed slightly early stages a faster decline antibodies infection Breakthrough mostly mild hospitalization was required less than 1% cases. Conclusions Most do not influence exhibit recall response cross-reactive clones towards new viral variants. or S1P greatly impaired, lesser extent those anti-TNF. Nevertheless, only few severe cases reported.

Language: Английский

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A unique human cord blood CD8⁺CD45RA⁺CD27⁺CD161⁺ T‐cell subset identified by flow cytometric data analysis using Seurat

Immunology, Journal Year: 2024, Volume and Issue: 173(1), P. 106 - 124

Published: May 26, 2024

Abstract Advances in single‐cell level analytical techniques, especially cytometric approaches, have led to profound innovation biomedical research, particularly the field of clinical immunology. This has resulted an expansion high‐dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable handle these challenges. Furthermore, most newly developed computational methods lack flexibility interoperability, hampering their accessibility usability. Here, we adapted Seurat, R package originally RNA sequencing (scRNA‐seq) analysis, flow data Based on a 20‐marker antibody panel analyses T‐cell profiles both adult blood cord (CB), showcased robust capacity Seurat which was further validated by Spectre, another package, conventional Importantly, identified unique CD8 + population defined as CD45RA CD27 CD161 T cell that predominantly present CB. We characterised its IFN‐γ‐producing potential cytotoxic properties using cytometry experiments scRNA‐seq from published dataset. Collectively, human CB subset demonstrated widely used possesses be repurposed facilitates thorough interpretation complicated single pipeline opens novel avenue data‐driven investigation

Language: Английский

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Longevity of antibody responses is associated with distinct antigen-specific B cell subsets early after infection

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

Published: Dec. 17, 2024

Upon infection, T cell-driven B cell responses in GC reactions induce memory cells and antibody-secreting that secrete protective antibodies. How formation of specifically long-lived plasma is regulated via the interplay between specific CD4+ not well understood. Generally, antibody levels decline over time after clearance primary infection.

Language: Английский

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A unique human cord blood CD8 + CD45RA + CD27 + CD161 + T cell subset identified by flow cytometric data analysis using Seurat

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 30, 2024

Advances in single-cell level analytical techniques, especially cytometric approaches, have led to profound innovation biomedical research, particularly the field of clinical immunology. This has resulted an expansion high-dimensional data, posing great challenges for comprehensive and unbiased analysis. Conventional manual analysis is thus becoming untenable handle these challenges. Furthermore, most newly developed computational methods lack flexibility interoperability, hampering their accessibility usability. Here, we adapted Seurat, R package originally RNA sequencing (scRNA-seq) analysis, flow data Based on a 20-marker antibody panel analyses T cell profiles both adult blood cord blood, showcased robust capacity Seurat which was further validated by Spectre, another package, conventional Importantly, identified unique CD8 population defined as CD45RA CD27 CD161 cell, that predominantly present blood. We characterized its IFN-γ-producing potential cytotoxic properties using cytometry experiments scRNA-seq from published dataset. Collectively, human subset demonstrated widely used possesses be repurposed facilitates thorough interpretation complicated single pipeline opens novel avenue data-driven investigation

Language: Английский

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Patient‐reported daily functioning after SARS‐CoV‐2 vaccinations in autoimmune neuromuscular diseases

European Journal of Neurology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Abstract Background and purpose There are concerns for safety regarding SARS‐CoV‐2 vaccines patients with autoimmune neuromuscular disease. We compared daily functioning using disease‐specific patient‐reported outcome measures (PROMs) before after vaccinations. Methods In this substudy of a prospective observational cohort study (Target‐to‐B!), myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), idiopathic myopathy (IIM) vaccinated against were included. Surveys (Myasthenia Gravis Activities Daily Living, Inflammatory Rasch‐Built Overall Disability Scale, Multifocal Motor Neuropathy Health Assessment Questionnaire–Disability Index) sent first vaccination every 60 days thereafter up to 12 months. Regression models constructed assess differences in PROM scores related vaccination, unrelated vaccination. also assessed the proportion deterioration at least minimal clinically important difference (MCID) between thereafter. Results included 325 (median age = 59 years, interquartile range 47–67, 156 [48%] female sex), whom 137 (42%) had MG, 79 (24%) CIDP, 43 (13%) MMN, 66 (20%) IIM. did not differ from paired PROMs, MCID was observed three 49 (6%) MG patients, none reported treatment change. eight 29 (28%), two (25%) Conclusions no effect on diseases, confirming its these patients.

Language: Английский

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Vaccination responses in B‐cell‐depleted multiple sclerosis patients: The role of drug pharmacokinetics

European Journal of Neurology, Journal Year: 2022, Volume and Issue: 29(11), P. 3137 - 3138

Published: Aug. 23, 2022

Language: Английский

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Immunosuppressive therapy selectively modulates B‐cell responses in patients with rheumatic and musculoskeletal diseases receiving the inactivated COVID‐19 vaccine

Rheumatology & autoimmunity, Journal Year: 2023, Volume and Issue: 3(2), P. 78 - 89

Published: June 1, 2023

Abstract Background Immunosuppressive medication reduces the immunogenicity of coronavirus disease 2019 (COVID‐19) vaccines in patients with rheumatic and musculoskeletal diseases (RMDs). However, underlying mechanism remains unclear. The primary aim our study was to dissect impact immunosuppressive on cellular humoral immune responses RMD receiving inactivated COVID‐19 vaccine. Methods A total 28 five healthy controls (HCs) two doses vaccine (Sinovac‐CoronaVac) were prospectively enrolled. Blood samples collected before vaccination (Week 0) one week after second 5). Neutralizing antibody (nAb) titers autoantibody measured by a pseudovirus‐based neutralization assay enzyme‐linked immunosorbent assay, respectively. CD4 + T‐cell CD19 B‐cell subsets serum cytokines analyzed flow cytometry. Results immunogenic HCs vaccination, but nAb lower than those HCs. Only systemic lupus erythematosus (SLE) had notably increased titers. Remarkably, IgG CD27 , IgG1 − B cells reduced, whereas cells, IgA markedly increased. Tfh cell Tfr produced not flare rate low comparable titers, unchanged T pro‐inflammatory (interleukin [IL]‐6, IL‐17, interferon‐γ, tumor necrosis factor‐α) vaccination. Conclusions therapy decreased maintained selectively modulating Optimization treatment regimen might ensure durable robust response.

Language: Английский

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Treatment with natalizumab and ocrelizumab in multiple sclerosis

Published: Oct. 25, 2023

In this thesis, our research regarding personalized treatment with natalizumab and ocrelizumab in multiple sclerosis (MS) by extending intervals the road towards implementation of a approach into clinical practice are outlined. Natalizumab highly effective treatments for reducing disease activity MS. Both approved standard intervals, while biological needs can vary between persons A approach, which tailored based on individual pharmacokinetic (PK) pharmacodynamic (PD) parameters, might lead way to optimizing current strategies. Personalizing reduce burden, potential risks, healthcare costs. For natalizumab, we detected several factors that influence PK. We found pregnancy subcutaneous administration were associated lower drug trough concentrations. These especially important consider when patients receive extended interval dosing (EID), where every four weeks is prolonged concentrations lower. It remains keep levels above therapeutic cut-off ensure adequate suppression MS activity. Measurement provide insight studied EID measurement adequately controlled. also showed be reliably measured finger prick, providing an alternative route collect blood samples. After evaluating wearing-off symptoms at end cycle, observed occurrence did not increase majority participants first year after EID. When discontinuing switching ocrelizumab, direct switch preferred sustained compared indirect bridging therapy. switching, neurologists should aware progressive multifocal leukoencephalopathy (PML), still develop discontinuation (carry-over PML). With regard described association concentrations, anti-drug antibodies, B-cells, enabling physicians predict optimal more precisely. considered concentration as good predictor SARS-CoV-2 vaccination response. B-cell counts during COVID-19 pandemic. The was able extend their without short-term Finally, using occur frequently similar characteristics symptoms. Other than BMI, there no predictors these Informing most likely possible uncertainty have To conclude, has become personalized. quest biomarker monitoring right both continues, promising study data its practice, further paving approach.

Language: Английский

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Longitudinal Dynamics of the SARS-CoV-2 Antibody Repertoire after SARS-CoV-2 Delta and Omicron Breakthrough Infections in Patients with Immune-Mediated Inflammatory Diseases

Published: Jan. 1, 2023

Background: Despite impaired humoral responses after SARS-CoV-2 vaccination, the incidence and severity of breakthrough infections is not increased in patients with immune-mediated inflammatory diseases (IMID) on immunosuppressants (ISPs). This could be explained by preserved recall but data are lacking. study aimed to investigate longitudinal dynamics response delta omicron IMID ISPs compared controls.Methods: a sub-study ongoing national Target-to-B! (T2B!) study, focusing vaccination patients. We included controls (IMID healthy individuals) who had completed primary vaccinations reported between July 1, 2021, April 2022, during prevalence variants. Antibody titers against wild-type RBD, S, RBD were measured at various time points post-infection assess responses. Dynamics assessed for separately, different controls.Findings: 480 participants. comparable following or infections. However, anti-CD20 therapy S1P modulators showed greatly those anti-TNF moderately greater decline antibodies than controls.Interpretations: Most do influence infections, exception modulators, lesser extent anti-TNF, which shows more rapid antibody decay.Funding: was supported ZonMw (The Netherlands Organization Health Research Development, grant 10430072010007). The sponsor no role design, analyses reporting study.Declaration Interest: F Eftimov T Kuijpers report (governmental) grants from immune SARS-Cov2 auto-immune diseases. also reports Prinses Beatrix Spierfonds, CSL Behring, Kedrion, Terumo BCT, Grifols, Takeda Pharmaceutical Company, GBS-CIDP Foundation; consulting fees UCB Pharma Behring; honoraria Grifols. AJ van der Kooi Behring participation an advisory board Argen-X. M Löwenberg Galapagos related this Bristol Myers Squibb, Pfizer, Takeda, Tillotts. Ph I Spuls involved performing clinical trials many pharmaceutical industries that manufacture drugs used treatment e.g. psoriasis atopic dermatitis, financial compensation paid department/hospital chief investigator TREAT NL registry taskforce SECURE-AD registry. M.W. Bekkenk secretary Dutch Experimental Dermatology Board head pigmentary disorders group within Board, Sanofi, Novartis Fondation René Touraine. J Killestein has speaking relationships Merck Serono, Biogen Idec, TEVA, Genzyme, Roche Novartis; Amsterdam UMC, location VUmc, MS Center received support research activities Bayer Shcering Pharma, GlaxoSmithKline, Roche, Teva, Novartis. B Horváth unpaid positions as medical advisor several patient groups, position ERN-SKIN, associate editor British Journal Dermatology; Abbvie, Akari Therapeutics, Celgene, Janssen-Cilag; Abbvie. J.J.G.M. Verschuuren Argenx, Alexion NMD Pharma; coinventor patent applications based MuSK-related research. DJ Hijnen AstraZeneca, Janssen, LEO Galderma, Lilly, Sanofi BIOMAP IMI. P.A. Doorn participated Octapharma. P. Paassen GSK; GSK Vifor boards. G.R.A.M. D'Haens Agomab, AM AMT, Arena Pharmaceuticals, Meiers Boehringer Ingelheim, Celltrion, Eli Exeliom Biosciences, Exo Biologics, Galapagos, Index Kaleido, Gilead, Glaxo Smith Kline, Gossamerbio, Immunic, Johnson Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus laboratories, Progenity, Protagonist; Arena, BMS, Takeda; boards Seres Health, AstraZeneca. R.B. Takkenberg Sobi Norgine Norgine. SH Goedee member Society Clinical Neurophysiology (unpaid), speaker Shire/Takeda. AH Zwinderman safety monitoring Torrent Ltd Foresee Pharmaceuticals Co. No other disclosures reported.Ethical Approval: ethical committee AMC (2020.194) approved study.

Language: Английский

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