T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination

Journal of Neurology Neurosurgery & Psychiatry, Год журнала: 2024, Номер 95(9), С. 855 - 864

Опубликована: Март 28, 2024

Background Messenger RNA (mRNA) vaccines provide robust protection against SARS-CoV-2 in healthy individuals. However, immunity after vaccination of patients with multiple sclerosis (MS) treated ocrelizumab (OCR), a B cell-depleting anti-CD20 monoclonal antibody, is not yet fully understood. Methods In this study, deep immune profiling techniques were employed to investigate the response induced by mRNA untreated MS (n=21), OCR-treated (n=57) and individuals (n=30). Results Among MS, 63% did produce detectable levels antibodies (non-seroconverted), those who have lower spike receptor-binding domain-specific IgG responses compared MS. Before vaccination, no discernible immunological differences observed between non-seroconverted seroconverted received overall more OCR infusions, had shorter intervals since their last infusion displayed higher serum concentrations at time initial vaccination. Following two vaccinations, smaller cell compartments but instead exhibited activation general CD4 + CD8 T compartments, as indicated upregulation CD38 HLA-DR surface expression, when patients. Conclusion These findings highlight importance optimising treatment regimens scheduling for maximise humoral cellular responses. This study provides valuable insights strategies including identification potential markers explore vaccine efficacy non-seroconverting

Язык: Английский

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mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses

Journal of Autoimmunity, Год журнала: 2024, Номер 144, С. 103175 - 103175

Опубликована: Фев. 21, 2024

SARS-CoV-2-specific CD8

Язык: Английский

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Long-Term Immune Response Profiles to SARS-CoV-2 Vaccination and Infection in People with Multiple Sclerosis on Anti-CD20 Therapy

Vaccines, Год журнала: 2023, Номер 11(9), С. 1464 - 1464

Опубликована: Сен. 7, 2023

Our objective was to analyze longitudinal cellular and humoral immune responses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection timing. PwMS (n = 439) BCDT (ocrelizumab, rituximab, ofatumumab) or immunotherapy were recruited for this prospective cohort study between June 2021 2022. SARS-CoV-2 spike-specific antibodies interferon-γ release CD4 CD8 T-cells upon stimulation spike protein peptide pools analyzed at different timepoints (after primary vaccination, 3 6 months after booster booster). Humoral response consistently lower whereas T-cell higher patients controls. Cellular decreased over time increased again significantly antibody titers than both untreated B-cell-depleted pwMS. led a significant increase SARS-CoV-2-specific responses. Despite attenuated responses, third seems recommendable, since least partial protection can be expected from strong response. Moreover, our data show that an assessment may helpful evaluate efficacy vaccination.

Язык: Английский

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Ocrelizumab Concentration Is a Good Predictor of SARS‐CoV‐2 Vaccination Response in Patients with Multiple Sclerosis

Annals of Neurology, Год журнала: 2022, Номер 93(1), С. 103 - 108

Опубликована: Окт. 17, 2022

Ocrelizumab, an anti-CD20 monoclonal antibody, counteracts induction of humoral immune responses after severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccinations in patients with multiple sclerosis (MS). We aimed to assess if serum ocrelizumab concentration measured at the time vaccination could predict response SARS-CoV-2 vaccination. In 52 MS, we found be a good predictor for IgG anti-RBD titers (comparable B-cell count). As course may predicted using pharmacokinetic models, this superior biomarker guide optimal timing depleted MS. ANN NEUROL 2023;93:103-108.

Язык: Английский

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Single‐cell multi‐omics analysis of COVID‐19 patients with pre‐existing autoimmune diseases shows aberrant immune responses to infection

European Journal of Immunology, Год журнала: 2023, Номер 54(1)

Опубликована: Окт. 6, 2023

Abstract In COVID‐19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre‐existing autoimmune conditions can therefore be at increased risk of severe COVID‐19 and/or associated sequelae, yet SARS‐CoV‐2 infection in this group has been little studied. Here, we performed single‐cell analysis peripheral blood mononuclear cells from patients three major diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during infection. We observed compositional differences between the disease groups coupled altered patterns gene expression, transcription factor activity, cell–cell communication that substantially shape response under While enrichment HLA‐DRlow CD14+ monocytes was all groups, type‐I interferon signaling as well inflammatory T cell monocyte varied widely patients. Our results reveal disturbed autoimmunity, highlighting important considerations for treatment follow‐up.

Язык: Английский

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Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

BMC Infectious Diseases, Год журнала: 2023, Номер 23(1)

Опубликована: Май 17, 2023

Abstract Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate against a primary infection in unvaccinated IMID patients ISPs. Methods active treatment ISPs controls (i.e. not ISP healthy controls) confirmed before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data infections registered using electronic surveys health records. A serum sample was collected measure anti-receptor-binding domain (RBD) antibodies. Results In total, 193 113 included. Serum samples 185 participants available, median time of 173 days between collection. The rate seropositive 78% compared 100% ( p < 0.001). Seropositivity rates lowest anti-CD20 (40.0%) anti-tumor necrosis factor (TNF) agents (60.5%), as other 0.001 0.001, respectively). Increased reported by 68 260 (26.2%; 95% CI 21.2–31.8%), leading intensification 6 out these (8.8%). Conclusion showed reduced infection, which mainly attributed anti-TNF agents. commonly, but mostly mild. Trial registration NL74974.018.20, ID: NL8900. Registered 9 September 2020.

Язык: Английский

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SARS-CoV-2 mRNA vaccine-induced immune responses in rheumatoid arthritis

Journal of Leukocyte Biology, Год журнала: 2023, Номер 114(4), С. 358 - 367

Опубликована: Июль 20, 2023

Our objective was to characterize T and B cell responses vaccination with SARS-CoV-2 antigens in immunocompromised rheumatoid arthritis (RA) patients. In 22 RA patients, clinical biological variables were analyzed before 4 weeks after each of 3 messenger RNA (mRNA) vaccine doses compared unmatched healthy individuals. Sequentially sampled peripheral blood mononuclear cells sera collected determine immune profiles analyze the response a spike peptide pool specificity receptor-binding domain (RBD). Anti-spike antibodies detectable 6 patients 1 dose increasing titers booster dose, although overall lower that control Responding first more likely have higher baseline proportion circulating follicular cells. mRNA elicited robust CD4+ following second doses. Consistent serologies, RBD-specific exhibited modest increase resulted marked increases only fraction both ancestral omicron RBD. results highlight importance multidose COVID-19 develop protective humoral response. However, these rapidly specific responses, despite delayed responses.

Язык: Английский

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Impact of methotrexate on humoral and cellular immune responses to SARS-CoV-2 mRNA vaccine in patients with rheumatoid arthritis

Clinical and Experimental Medicine, Год журнала: 2023, Номер 23(8), С. 4707 - 4720

Опубликована: Авг. 16, 2023

Язык: Английский

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T follicular helper cell responses to SARS‐CoV ‐2 vaccination among healthy and immunocompromised adults

Immunology and Cell Biology, Год журнала: 2023, Номер 101(6), С. 504 - 513

Опубликована: Фев. 24, 2023

Abstract The worldwide rollout of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccinations in the last years has produced a multitude studies investigating T‐cell responses peripheral blood and limited number secondary lymphoid tissues. As key component to an effective immune response, vaccine‐specific T follicular helper (Tfh) cells are localized draining lymph node (LN) assist selection highly specific B‐cell clones for production neutralizing antibodies. While these have been noted as circulating Tfh (cTfh) cells, they not often taken into consideration when examining CD4 + responses, particularly immunocompromised groups. Furthermore, site‐specific analyses locations such LN recently become attractive area investigation. This is mainly result improved sampling methods via ultrasound‐guided fine‐needle biopsy (FNB)/fine‐needle aspiration (FNA), which less invasive than excision able be performed longitudinally. undertaken healthy individuals, data from groups lacking. review will focus on both cTfh after SARS‐CoV‐2 vaccination individuals. investigation could identify characteristics successful response required prevention infection viral clearance. furthermore may highlight that fine‐tuned improve vaccine efficacy within at risk more disease.

Язык: Английский

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

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Дек. 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.

Язык: Английский

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