Qingqing Zhu1, Yun Li1, Lili Zhang1, Min Wang1, Zhongxin Chen2, Junxiang Shi3, Ji Li3, Baiqing Li4, Zhijun Li1, Yuanyuan Wang5, Changhao Xie6,7. 1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. 2. Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. 3. Department of Clinical Medicine, Bengbu Medical College, Bengbu, 233003, China. 4. Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical College, Bengbu, 233003, China. 5. Department of Histology and Embryology, Bengbu Medical College, Bengbu, 233003, China. wangyuanyuantcm@126.com. 6. Department of Rheumatology and Immunology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, China. uglboy2002@126.com. 7. Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Bengbu Medical College, Bengbu, 233003, China. uglboy2002@126.com.
Abstract
BACKGROUND: At present, anti-CD20 monoclonal antibody treatments targeting systemic lupus erythematosus (SLE) are complex, variable, and often have disappointing outcomes. High levels of programmed cell death-1 (PD-1) and its ligands (PD-L1, PD-L2) or CD80/CD86 on B cell surfaces are markers of increased B cell activity. However, their expression levels on CD19+CD20+/- B cells and their clinical significance for SLE dynamics have not been carefully investigated. METHODS: Flow cytometry was used to detect the expression levels of PD-1, PD-L1, PD-L2, CD80, and CD86 on CD19+CD20+/- B cells in peripheral blood from SLE patients and healthy controls (HCs). The amount of anti-dsDNA and immunoglobin G (IgG) secreted by CD19+CD20+/- B cells was measured by enzyme-linked immunosorbent assay. RESULTS: CD19+CD20- B cell frequency was significantly higher in SLE patients than in HCs (P < 0.001), and was positively correlated with disease activity. In SLE patients, frequencies of PD-1, PD-L1, PD-L2, and CD86 on CD19+CD20- B cells were significantly higher than CD19+CD20+ B cells (P ≤ 0.002) and were significantly correlated with individual laboratory and clinically based parameters (P < 0.05). In vitro tests, we found that the levels of anti-dsDNA and IgG secreted by CD19+CD20- B cells from patients with SLE were significantly higher than the HC group (P < 0.05). CONCLUSIONS: We found abnormal frequency of CD19+CD20- B cells and increased expression of surface markers on these cells from SLE patients. And the CD19+CD20- B cells had the ability to proliferate and secrete anti-dsDNA and IgG. Additionally, our results suggested that CD19+CD20- B cells from SLE patients may be the activated B cells and caused poor efficacy of rituximab. Key Points • CD19+CD20- B cell frequencies were significantly higher in SLE patients. • Frequencies of PD-1 and its ligands on CD19+CD20- B cells increased significantly in SLE patients. • CD19+CD20- B cells in SLE patients had the ability to secrete anti-dsDNA and IgG. • CD19+CD20- B cells in SLE patients may be the activated B cells and caused poor efficacy of rituximab.
BACKGROUND: At present, anti-CD20 monoclonal antibody treatments targeting systemic lupus erythematosus (SLE) are complex, variable, and often have disappointing outcomes. High levels of programmed cell death-1 (PD-1) and its ligands (PD-L1, PD-L2) or CD80/CD86 on B cell surfaces are markers of increased B cell activity. However, their expression levels on CD19+CD20+/- B cells and their clinical significance for SLE dynamics have not been carefully investigated. METHODS: Flow cytometry was used to detect the expression levels of PD-1, PD-L1, PD-L2, CD80, and CD86 on CD19+CD20+/- B cells in peripheral blood from SLEpatients and healthy controls (HCs). The amount of anti-dsDNA and immunoglobin G (IgG) secreted by CD19+CD20+/- B cells was measured by enzyme-linked immunosorbent assay. RESULTS:CD19+CD20- B cell frequency was significantly higher in SLEpatients than in HCs (P < 0.001), and was positively correlated with disease activity. In SLEpatients, frequencies of PD-1, PD-L1, PD-L2, and CD86 on CD19+CD20- B cells were significantly higher than CD19+CD20+ B cells (P ≤ 0.002) and were significantly correlated with individual laboratory and clinically based parameters (P < 0.05). In vitro tests, we found that the levels of anti-dsDNA and IgG secreted by CD19+CD20- B cells from patients with SLE were significantly higher than the HC group (P < 0.05). CONCLUSIONS: We found abnormal frequency of CD19+CD20- B cells and increased expression of surface markers on these cells from SLEpatients. And the CD19+CD20- B cells had the ability to proliferate and secrete anti-dsDNA and IgG. Additionally, our results suggested that CD19+CD20- B cells from SLEpatients may be the activated B cells and caused poor efficacy of rituximab. Key Points • CD19+CD20- B cell frequencies were significantly higher in SLEpatients. • Frequencies of PD-1 and its ligands on CD19+CD20- B cells increased significantly in SLEpatients. • CD19+CD20- B cells in SLEpatients had the ability to secrete anti-dsDNA and IgG. • CD19+CD20- B cells in SLEpatients may be the activated B cells and caused poor efficacy of rituximab.
Entities:
Keywords:
Autoantibody; B cell; Surface marker; Systemic lupus erythematosus
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