Altered B cell balance, but unaffected B cell capacity to limit monocyte activation in anti-neutrophil cytoplasmic antibody-associated vasculitis in remission
Autor: | Peter Heeringa, Coen A. Stegeman, Cees G. M. Kallenberg, Abraham Rutgers, Nikola Lepse, Wayel H. Abdulahad |
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Přispěvatelé: | Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR) |
Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Male
ANCA-ASSOCIATED VASCULITIS CD38 Monocytes DISEASE CONSENSUS CONFERENCE Pharmacology (medical) Aged 80 and over B-Lymphocytes Regulatory education.field_of_study medicine.diagnostic_test biology Remission Induction MULTIPLE-SCLEROSIS Middle Aged Flow Cytometry POLYANGIITIS WEGENERS Interleukin-10 Interleukin 10 medicine.anatomical_structure IL-10 Female Adult medicine.medical_specialty Prednisolone Regulatory B cells Population B-Lymphocyte Subsets EFFECTOR Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis CD19 Immunophenotyping Flow cytometry WEGENERS-GRANULOMATOSIS Rheumatology Internal medicine medicine Humans RITUXIMAB education Cyclophosphamide B cell Aged SUPPRESSION B cells Tumor Necrosis Factor-alpha business.industry Monocyte regulatory B cells Coculture Techniques Lymphocyte Subsets Endocrinology Case-Control Studies Immunology biology.protein T-CELLS business |
Zdroj: | Rheumatology, 53(9), 1683-1692. Oxford University Press |
ISSN: | 1462-0324 |
Popis: | OBJECTIVE: Regulatory B cells (Bregs) constitute a subset of B cells with immunomodulatory properties. Numerical and functional alterations in the Breg compartment have been associated with autoimmunity. The aim of this study was to assess the frequency and function of Bregs in patients with ANCA-associated vasculitis (AAV).METHODS: B cell subsets were determined in the peripheral blood of 48 AAV patients (12 active, 36 in remission) and 41 healthy controls (HCs) by flow cytometry. Bregs were defined within the CD19(+) population as CD24(hi)CD38(hi) or CD24(hi)CD27(+) cells. The percentage of IL-10-positive B cells in circulation was analysed by flow cytometry. Sorted CD19(+) B cells were co-cultured with monocytes to evaluate their capacity to inhibit monocyte TNF-α production upon lipopolysaccharide stimulation.RESULTS: The frequency of circulating CD19(+)CD24(hi)CD38(hi) cells was not different in AAV patients in remission compared with HCs, but was decreased in patients with active disease [mean in HCs 5.5% (s.d. 1.6) vs active 3.8% (s.d. 2.8), P = 0.0104]. Furthermore, the percentage of CD19(+)CD24(hi)CD27(+) cells was significantly decreased in both remission and active patients when compared with HCs [HCs 15.0% (s.d. 9.3) vs remission 6.6% (s.d. 4.4) (P < 0.0001) vs active 6.4% (s.d. 6.2) (P = 0.0006)]. The frequency of IL-10-positive B cells was comparable between patients and HCs. B cells from AAV patients suppressed monocyte TNF-α production to a similar extent to cells from HCs.CONCLUSION: Based on immunophenotypic classification, Bregs are numerically diminished in AAV patients. However, B cell function in terms of IL-10 production and their capacity to suppress monocyte activation is not compromised in AAV patients in remission. |
Databáze: | OpenAIRE |
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