Academic Journal
IgA class-switched CD27-CD21+ B cells in IgA nephropathy.
| Τίτλος: | IgA class-switched CD27-CD21+ B cells in IgA nephropathy. |
|---|---|
| Συγγραφείς: | Popova A; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.; Department of Internal Medicine, University of Latvia, Riga, Latvia., Slisere B; Joint Laboratory, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Doctoral Studies, Riga Stradins University, Riga, Latvia., Racenis K; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Kuzema V; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Karklins R; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Saulite M; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Seilis J; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia., Saulite AJ; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia., Vasilvolfa A; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Internal Medicine, University of Latvia, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Vaivode K; Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia., Pjanova D; Institute of Microbiology and Virology, Riga Stradins University, Riga, Latvia., Kroica J; Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia., Cernevskis H; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Lejnieks A; Department of Internal Diseases, Riga Stradins University, Riga, Latvia.; Riga East Clinical University Hospital, Riga, Latvia., Petersons A; Department of Nephrology, Pauls Stradins Clinical University Hospital, Riga, Latvia.; Department of Internal Diseases, Riga Stradins University, Riga, Latvia., Oleinika K; Department of Internal Diseases, Riga Stradins University, Riga, Latvia.; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical, School, Boston, MA, USA. |
| Πηγή: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2025 Feb 28; Vol. 40 (3), pp. 505-515. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8706402 Publication Model: Print Cited Medium: Internet ISSN: 1460-2385 (Electronic) Linking ISSN: 09310509 NLM ISO Abbreviation: Nephrol Dial Transplant Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Oxford University Press Original Publication: [Berlin ; New York, NY] : Springer International, [c1986- |
| Ιατρικοί όροι (MeSH): | Glomerulonephritis, IGA*/immunology , Glomerulonephritis, IGA*/metabolism , Glomerulonephritis, IGA*/pathology , Immunoglobulin A*/immunology , B-Lymphocytes*/immunology , B-Lymphocytes*/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 7*/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 7*/immunology , Receptors, Complement 3d*/metabolism , Receptors, Complement 3d*/immunology , Immunoglobulin Class Switching*/immunology, Humans ; Male ; Female ; Adult ; Case-Control Studies ; Middle Aged ; Prognosis ; Lymphocyte Activation ; Flow Cytometry ; Follow-Up Studies |
| Περίληψη: | Background: Immunoglobulin A nephropathy (IgAN) is characterized by the production of galactose-deficient IgA1 (GdIgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA secretion remain unknown. Methods: We carried out flow cytometry analysis of peripheral blood B cells in patients with IgAN and control subjects with a focus on IgA-expressing B cells to uncover the pathways of B cell activation in IgAN and how these could give rise to pathogenic GdIgA1 antibodies. Results: In addition to global changes in the B cell landscape-expansion of naïve and reduction in memory B cells-IgAN patients present with an increased frequency of IgA-expressing B cells that lack the classical memory marker CD27, but are CD21+. IgAN patients furthermore have an expanded population of IgA+ antibody-secreting cells, which correlate with serum IgA levels. Both IgA+ plasmabalsts and CD27- B cells co-express GdIgA1. Implicating dysregulation at mucosal surfaces as the driver of such B cell differentiation, we found a correlation between lipopolysaccharide in the serum and IgA+CD27- B cell frequency. Conclusion: We propose that dysregulated immunity in the mucosa may drive de novo B cell activation within germinal centres, giving rise to IgA+CD27- B cells and subsequently IgA-producing plasmablasts. These data integrate B cells into the paradigm of IgAN pathogenesis and allow further investigation of this pathway to uncover biomarkers and develop therapeutic interventions. (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.) |
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| Grant Information: | lzp-2019/1-0139 Latvian Council of Science |
| Contributed Indexing: | Keywords: B cells; IgA nephropathy; IgA-producing plasmablasts; antibodies; disease mechanisms |
| Substance Nomenclature: | 0 (Immunoglobulin A) 0 (Tumor Necrosis Factor Receptor Superfamily, Member 7) 0 (Receptors, Complement 3d) |
| Entry Date(s): | Date Created: 20240717 Date Completed: 20250423 Latest Revision: 20250514 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11879059 |
| DOI: | 10.1093/ndt/gfae173 |
| PMID: | 39020236 |
| Βάση Δεδομένων: | MEDLINE |
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