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Skewed peripheral B- and T-cell compartments in patients with ANCA-associated vasculitis.
- Source :
-
Rheumatology (Oxford, England) [Rheumatology (Oxford)] 2021 May 14; Vol. 60 (5), pp. 2157-2168. - Publication Year :
- 2021
-
Abstract
- Objectives: To characterize lymphocytes dysregulation in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).<br />Methods: Using flow cytometry, we analysed B- and T-cell subsets in peripheral blood from 37 untreated patients with active disease (29 GPA and 8 MPA) and 22 healthy controls (HCs).<br />Results: GPA patients had increased Th2 (1.8 vs 1.0%, P = 0.02), Th9 (1.1 vs 0.2%, P = 0.0007) and Th17 (1.4 vs 0.9%, P = 0.03) cells compared with HC. Patients with MPO-ANCAs had significantly more CD21- B cells than HC or PR3-ANCA patients (6.9 vs 3.3% and 4.4%, P = 0.01). CD69 expressing B cells were significantly higher in GPA and MPA (3.0 and 5.9 vs 1.4%, P = 0.02 and P = 0.03, respectively) compared with HC, whereas B-cell activating factor-receptor expression was decreased in GPA and MPA (median fluorescence intensity ratio 11.8 and 13.7 vs 45.1 in HC, P < 0.0001 and P = 0.003, respectively). Finally, IL-6-producing B cells were increased in GPA vs HC (25.8 vs 14.9%, P < 0.0001) and decreased in MPA vs HC (4.6 vs 14.9%, P = 0.005), whereas TNF-α-producing B cells were lower in both GPA and MPA patients compared with controls (15 and 8.4 vs 30%, P = 0.01 and P = 0.006, respectively).<br />Conclusion: Skewed T-cell polarization towards Th2, Th9 and Th17 responses characterizes GPA, whereas B-cell populations are dysregulated in both GPA and MPA with an activated phenotype and a decreased B-cell activating factor-receptor expression. Finally, inflammatory B cells producing IL-6 are dramatically increased in GPA, providing an additional mechanism by which rituximab could be effective.<br /> (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- B-Lymphocytes metabolism
Cytokines metabolism
Flow Cytometry
Granulomatosis with Polyangiitis immunology
Granulomatosis with Polyangiitis metabolism
Humans
Microscopic Polyangiitis immunology
Microscopic Polyangiitis metabolism
T-Lymphocytes metabolism
B-Lymphocytes immunology
Granulomatosis with Polyangiitis blood
Microscopic Polyangiitis blood
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1462-0332
- Volume :
- 60
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Rheumatology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 33026090
- Full Text :
- https://doi.org/10.1093/rheumatology/keaa432