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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Bakhtiar, S; Kaffenberger, C; Salzmann-Manrique, E; Donhauser, S; Lueck, L; Karaca, NE; Gonzalez-Granado, LI; Hazar, E; Keles, S; Seidel, MG; Fekadu, J; Königs, C; Schubert, R; Bader, P; Huenecke, S.
Regulatory B cells in patients suffering from inborn errors of immunity with severe immune dysregulation.
J Autoimmun. 2022; 132:102891 Doi: 10.1016/j.jaut.2022.102891
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Seidel Markus
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Abstract:: BACKGROUND: 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 CD21^low expressing B cells of patients with LRBA deficiency (N = 6) and non-LRBA deficiency IEI (N = 13) with overlapping clinical symptoms of immune dysregulation. Normal values for Breg subpopulations were obtained from patients age-matched healthy cohorts (N = 48). Furthermore, we investigated the impact of abatacept treatment in LRBA deficient patients receiving biweekly abatacept (N = 5). METHODS: Using a flow cytometric approach with a pre-formulated antibody panel in peripheral blood samples, Breg subsets including plasmablasts (CD27⁺CD38^hi), transitional B cells (CD24^hiCD38^hi), and B10 cells (CD24^hiCD27⁺), and additionally the CD21^low B cells (CD21^lowCD38^low) were analyzed. Breg function was assessed by the interleukin-10 expression within the CD19⁺ 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 = 0.031) and B10 cells (P = 0.031) as well as a tendency towards higher CD21^low B cells (P = 0.063). Within the non-LRBA deficient cohort, we observe a significant expansion of the plasmablasts (P = 0.012), and a tendency towards elevated levels of CD21^low expressing B cells (P = 0.063). The treatment with abatacept ameliorated disease symptoms in the LRBA deficient cohort and led to an effective decrease in CD21^low B cells over time (P = 0.021). Furthermore, there was a significantly increased level of B cell-activating factor (BAFF; P = 0.02) and lower IL-12p70 secretion upon stimulation (P = 0.020) in the LRBA cohort. CONCLUSION: Aberrant maturation of Breg subsets and the pathological expansion of CD21^low 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 CD21^low B cells. Abatacept treatment results in a steady decrease in CD21^low B cells.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; B-Lymphocytes, Regulatory - administration & dosage; Abatacept - administration & dosage; Plasma Cells - administration & dosage; Flow Cytometry - administration & dosage; Autoimmune Diseases - diagnosis, drug therapy; Adaptor Proteins, Signal Transducing - administration & dosage
Find related publications in this database (Keywords): B regulatory cells; Inborn error of immunity; LRBA; CD21 low B cell; B10 cells; Abatacept