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
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