Regulatory B cells in patients suffering from inborn errors of immunity with severe immune dysregulation

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dc.contributor.authorBakhtiar, Shahrzad
dc.contributor.authorKaffenberger, Celia
dc.contributor.authorSalzmann-Manrique, Emilia
dc.contributor.authorDonhauser, Sabine
dc.contributor.authorLueck, Leon
dc.contributor.authorKaraca, Neslihan Edeer
dc.contributor.authorGonzalez-Granado, Luis, I
dc.date.accessioned2024-02-23T14:12:33Z
dc.date.available2024-02-23T14:12:33Z
dc.date.issued2022
dc.departmentNEÜen_US
dc.description.abstractBackground: Immune dysregulation as a result of an inborn error of immunity (IEI) leads to the complicated symptoms of refractory multi-organ immune dysregulation. B lymphocytes with immune regulatory capacity (Breg) are activated by environmental triggers and act as regulators of the immune response as observed in several autoimmune diseases.Objective: We sought to investigate the Breg profile and the CD21low expressing B cells of patients with LRBA deficiency (N symbolscript 6) and non-LRBA deficiency IEI (N symbolscript 13) with overlapping clinical symptoms of immune dys-regulation. Normal values for Breg subpopulations were obtained from patients age-matched healthy cohorts (N symbolscript 48). Furthermore, we investigated the impact of abatacept treatment in LRBA deficient patients receiving biweekly abatacept (N symbolscript 5).Methods: Using a flow cytometric approach with a pre-formulated antibody panel in peripheral blood samples, Breg subsets including plasmablasts symbolscript transitional B cells (CD24hiCD38hi), and B10 cells symbolscript and additionally the CD21low B cells (CD21lowCD38low) were analyzed. Breg function was assessed by the interleukin-10 expression within the symbolscript population. Additionally, B cell cytokines were measured in cell culture supernatants. Results: We observe significant alterations of B cell/Breg subpopulations in the LRBA deficient cohort including a severe lack of memory B cells (P symbolscript 0.031) and B10 cells (P symbolscript 0.031) as well as a tendency towards higher CD21low B cells (P symbolscript 0.063). Within the non-LRBA deficient cohort, we observe a significant expansion of the plasmablasts (P symbolscript 0.012), and a tendency towards elevated levels of CD21low expressing B cells (P symbolscript 0.063). The treatment with abatacept ameliorated disease symptoms in the LRBA deficient cohort and led to an effective decrease in CD21low B cells over time (P symbolscript 0.021). Furthermore, there was a significantly increased level of B cell-activating factor (BAFF; P symbolscript 0.02) and lower IL-12p70 secretion upon stimulation (P symbolscript 0.020) in the LRBA cohort.Conclusion: Aberrant maturation of Breg subsets and the pathological expansion of CD21low B cells in patients with IEI may have therapeutic implications. Patients suffering from LRBA deficiency show a lack of memory B cells, insufficient expansion of B10 cells, increased BAFF levels as well as an increase in circulating CD21low B cells. Abatacept treatment results in a steady decrease in CD21low B cells.en_US
dc.description.sponsorshipUniversity Hospital Frankfurt, Germanyen_US
dc.description.sponsorshipThis work was funded by the University Hospital Frankfurt, Germany. Authors have no conflict of interest.en_US
dc.identifier.doi10.1016/j.jaut.2022.102891
dc.identifier.issn0896-8411
dc.identifier.issn1095-9157
dc.identifier.pmid36113303en_US
dc.identifier.scopus2-s2.0-85137660480en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.jaut.2022.102891
dc.identifier.urihttps://hdl.handle.net/20.500.12452/12105
dc.identifier.volume132en_US
dc.identifier.wosWOS:000862694500001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherAcademic Press Ltd- Elsevier Science Ltden_US
dc.relation.ispartofJournal Of Autoimmunityen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectB Regulatory Cellsen_US
dc.subjectInborn Error Of Immunityen_US
dc.subjectLrbaen_US
dc.subjectCd21 Low B Cellen_US
dc.subjectB10 Cellsen_US
dc.subjectAbatacepten_US
dc.titleRegulatory B cells in patients suffering from inborn errors of immunity with severe immune dysregulationen_US
dc.typeArticleen_US

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