Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients
Objective: Radiographic axial spondyloarthritis (r-axSpA) is a chronic rheumatic disease in which innate immune cells and T cells are thought to play a major role. However, recent studies also hint at B cell involvement. Here, we performed an in-depth analysis on alterations within the B-cell compar...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-06-01
|
| Series: | Journal of Translational Autoimmunity |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258990902500005X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573094682689536 |
|---|---|
| author | Rick Wilbrink Stefan F.H. Neys Rudi W. Hendriks Anneke Spoorenberg Frans G.M. Kroese Odilia B.J. Corneth Gwenny M.P.J. Verstappen |
| author_facet | Rick Wilbrink Stefan F.H. Neys Rudi W. Hendriks Anneke Spoorenberg Frans G.M. Kroese Odilia B.J. Corneth Gwenny M.P.J. Verstappen |
| author_sort | Rick Wilbrink |
| collection | DOAJ |
| description | Objective: Radiographic axial spondyloarthritis (r-axSpA) is a chronic rheumatic disease in which innate immune cells and T cells are thought to play a major role. However, recent studies also hint at B cell involvement. Here, we performed an in-depth analysis on alterations within the B-cell compartment from r-axSpA patients. Methods: We performed immune gene expression profiling on total peripheral blood B cells from 8 r-axSpA patients and 8 healthy controls (HCs). Next, we explored B cell subset distribution and B-cell receptor (BCR) signaling responses in circulating B cells from 28 r-axSpA patients and 15 HCs, by measuring spleen tyrosine kinase, phosphoinositide 3-kinase and extracellular signal regulated kinase 1/2 phosphorylation upon α-Ig stimulation using phosphoflow cytometry. Results: Immune gene expression profiling indicated an elevated pathway score for BCR signaling in total B cells from r-axSpA patients compared with HCs. Flow cytometric analysis revealed an increase in frequency of both total and double-negative 2 (DN2) B cells in r-axSpA patients compared with HCs. In r-axSpA patients, DN2 B cells displayed an isotype shift towards IgA. Remarkably, where DN2 B cells from HCs were hyporesponsive, these cells displayed significant proximal BCR signaling responses in r-axSpA patients. Enhanced BCR signaling responses were also observed in the transitional and naïve B cell population from r-axSpA patients compared with HCs. The enhanced BCR signaling responses in DN2 B cells correlated with clinical disease parameters. Conclusion: In r-axSpA patients, circulating DN2 B cells are expanded and, together with transitional and naïve B cells, display significantly enhanced BCR signaling responses upon stimulation. Together, our data suggest B cell involvement in the pathogenesis of r-axSpA. |
| format | Article |
| id | doaj-art-9be1494ff412499bbf1716f091d9edd8 |
| institution | Kabale University |
| issn | 2589-9090 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-9be1494ff412499bbf1716f091d9edd82025-02-02T05:29:11ZengElsevierJournal of Translational Autoimmunity2589-90902025-06-0110100270Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patientsRick Wilbrink0Stefan F.H. Neys1Rudi W. Hendriks2Anneke Spoorenberg3Frans G.M. Kroese4Odilia B.J. Corneth5Gwenny M.P.J. Verstappen6Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Pulmonary Medicine, Erasmus MC, University Medical Center, Rotterdam, The NetherlandsDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Corresponding author. Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, PO-Box 30.001, 9700 RB, Groningen, The Netherlands.Objective: Radiographic axial spondyloarthritis (r-axSpA) is a chronic rheumatic disease in which innate immune cells and T cells are thought to play a major role. However, recent studies also hint at B cell involvement. Here, we performed an in-depth analysis on alterations within the B-cell compartment from r-axSpA patients. Methods: We performed immune gene expression profiling on total peripheral blood B cells from 8 r-axSpA patients and 8 healthy controls (HCs). Next, we explored B cell subset distribution and B-cell receptor (BCR) signaling responses in circulating B cells from 28 r-axSpA patients and 15 HCs, by measuring spleen tyrosine kinase, phosphoinositide 3-kinase and extracellular signal regulated kinase 1/2 phosphorylation upon α-Ig stimulation using phosphoflow cytometry. Results: Immune gene expression profiling indicated an elevated pathway score for BCR signaling in total B cells from r-axSpA patients compared with HCs. Flow cytometric analysis revealed an increase in frequency of both total and double-negative 2 (DN2) B cells in r-axSpA patients compared with HCs. In r-axSpA patients, DN2 B cells displayed an isotype shift towards IgA. Remarkably, where DN2 B cells from HCs were hyporesponsive, these cells displayed significant proximal BCR signaling responses in r-axSpA patients. Enhanced BCR signaling responses were also observed in the transitional and naïve B cell population from r-axSpA patients compared with HCs. The enhanced BCR signaling responses in DN2 B cells correlated with clinical disease parameters. Conclusion: In r-axSpA patients, circulating DN2 B cells are expanded and, together with transitional and naïve B cells, display significantly enhanced BCR signaling responses upon stimulation. Together, our data suggest B cell involvement in the pathogenesis of r-axSpA.http://www.sciencedirect.com/science/article/pii/S258990902500005XAxial spondyloarthritisRadiographic axial spondyloarthritisAnkylosing spondylitisB cellsB cell receptor (BCR) signalingPhosphoflow cytometry |
| spellingShingle | Rick Wilbrink Stefan F.H. Neys Rudi W. Hendriks Anneke Spoorenberg Frans G.M. Kroese Odilia B.J. Corneth Gwenny M.P.J. Verstappen Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients Journal of Translational Autoimmunity Axial spondyloarthritis Radiographic axial spondyloarthritis Ankylosing spondylitis B cells B cell receptor (BCR) signaling Phosphoflow cytometry |
| title | Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients |
| title_full | Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients |
| title_fullStr | Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients |
| title_full_unstemmed | Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients |
| title_short | Aberrant B cell receptor signaling responses in circulating double-negative 2 B cells from radiographic axial spondyloarthritis patients |
| title_sort | aberrant b cell receptor signaling responses in circulating double negative 2 b cells from radiographic axial spondyloarthritis patients |
| topic | Axial spondyloarthritis Radiographic axial spondyloarthritis Ankylosing spondylitis B cells B cell receptor (BCR) signaling Phosphoflow cytometry |
| url | http://www.sciencedirect.com/science/article/pii/S258990902500005X |
| work_keys_str_mv | AT rickwilbrink aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT stefanfhneys aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT rudiwhendriks aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT annekespoorenberg aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT fransgmkroese aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT odiliabjcorneth aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients AT gwennympjverstappen aberrantbcellreceptorsignalingresponsesincirculatingdoublenegative2bcellsfromradiographicaxialspondyloarthritispatients |