Characterization of Regulatory B cells in Patients with Anti-Neutrophil Cytoplasmic Autoantibody Vasculitis
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Aybar, Lydia. Characterization of Regulatory B Cells In Patients with Anti-neutrophil Cytoplasmic Autoantibody Vasculitis. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School, 2015. https://doi.org/10.17615/d7s4-de44APA
Aybar, L. (2015). Characterization of Regulatory B cells in Patients with Anti-Neutrophil Cytoplasmic Autoantibody Vasculitis. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/d7s4-de44Chicago
Aybar, Lydia. 2015. Characterization of Regulatory B Cells In Patients with Anti-Neutrophil Cytoplasmic Autoantibody Vasculitis. Chapel Hill, NC: University of North Carolina at Chapel Hill Graduate School. https://doi.org/10.17615/d7s4-de44- Last Modified
- March 19, 2019
- Creator
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Aybar, Lydia
- Affiliation: School of Medicine, Department of Microbiology and Immunology
- Abstract
- ANCA-associated vasculitis (AAV) is B cell dependent; however, which B cell subsets modulate immunopathogenesis remains unknown. Although their phenotype is controversial, regulatory B cells (Bregs) play a critical role in immunological tolerance via secretion of IL-10. In this study, we investigate three B cell phenotypes reported to produce IL-10: CD5+, CD24hiCD38hi and CD24hiCD27+ B cells in patients with AAV. We further analyzed the CD5+ subsets of the CD24hiCD38hi and CD24hiCD27+ B cell populations. In our first investigation, we discovered a lower percentage of CD5+ B cells in patients with active AAV, whereas the percentage of CD5+ B cells from patients in remission was indistinguishable from healthy controls (HCs). After rituximab, median time to relapse was 31 months in patients maintaining a normalized percentage of CD5+ B cells with or without maintenance immunosuppression. Among patients whose B cells repopulated with a low or sharply declining percentage of CD5, those who were on low or no maintenance immunosuppression relapsed sooner (median 17 months) than patients who were maintained on high levels of oral maintenance immunosuppression (29 months; p=0.002). The second phase of our investigation identified that the CD5+ subset of CD24hiCD38hi B cells was decreased in patients with active disease relative to patients in remission (p≤0.001) and HCs (p≤0.0001). B cells from patients with active disease produced less IL-10 than those from patients in remission (p=0.005) and HCs (p=0.001). As IL-10+, CD5+CD24hiCD38hi and CD24hiCD38hi B cells increased in disease remission within an individual, ANCA titers decreased. The CD5+ subset of CD24hiCD38hi B cells decreased in active disease and rebounded during remission similarly to IL-10-producing B cells, suggesting that CD5 may identify functional IL-10-producing Bregs. These data indicate that Bregs malfunction during active disease due to reduced IL-10 expression, permitting ANCA production. CD5+ B cells, specifically the CD5+ subset of CD24hiCD38hi, may be useful indicators of disease activity, remission, and future relapse. These Breg subsets may be used to guide remission maintenance therapy after rituximab treatment to balance immunological B cell tolerance, maintain beneficial B cells, reduce pathogenic ANCA production, and sustain remission with minimal therapeutic interventions.
- Date of publication
- May 2015
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- In Copyright
- Advisor
- Su, Maureen
- Tedder, Thomas
- Clarke, Stephen H.
- Falk, Ronald J.
- Peden, David
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2015
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- Place of publication
- Chapel Hill, NC
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- There are no restrictions to this item.
- Date uploaded
- June 23, 2015
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