Advances of using antibody against B cell activating factor for treatment of autoimmune diseases / 生物工程学报

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.

Expression of BAFF and BR3 in patients with systemic lupus erythematosus

The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment.

Expression of BAFF and its specific receptor BAFF-R in patients with B-cell non-Hodgkin′s lympho-ma and their significance / 中华微生物学和免疫学杂志

Objective To investigate the expression of B-cell activating factor ( BAFF ) and its specific receptor BAFF-R in patients with B-cell non-Hodgkin′s lymphoma ( B-NHL) and to analyze the cor-relations between BAFF and the development of B-NHL.Methods RTQ-PCR and Western blot assay were used to measure the expression of BAFF and its specific receptor BAFF-R in patients with B-NHL.Fluores-cence immunocytochemical staining was used to determine the localization of BAFF and BAFF-R in Raji cells, a B-NHL cell line.The expression of BAFF in tumor tissues from patients with B-NHL of different his-tologic subtypes was measured by immunohistochemistry.WST proliferation and TUNEL assays were used to evaluate the effects of BAFF and BAFF-R on the proliferation, survival rate and apoptosis of Raji cells.Lin-ear correlations between the concentrations of lactate dehydrogenase ( LDH) and the expression of BAFF and BAFF at mRNA and protein levels in patients with B-NHL were analyzed.Results BAFF and its specific receptor BAFF-R were expressed in Raji cells and played an important role in the survival and proliferation of B-NHL cell line.The expression of BAFF in tumor cells from patients with B-NHL varied with the different histologic subtypes of B-NHL.Patients with small B-cell malignant lymphoma, large B-cell lymphoma ( LBCL) , mucosa-associated lymphoid tissue lymphoma ( MALT lymphoma) and follicular lymphoma showed higher levels of BAFF, while those with mantle cell lymphoma showed lower levels of BAFF.Compared with the healthy subjects, patients with B-NHL showed significantly increased expression of BAFF at mRNA and protein levels.The levels of LDH were closely related to the expression of BAFF at mRNA and protein lev-els.Conclusion BAFF and its specific receptor BAFF-R might play an important role in the growth and survival of malignant B cells.

IFN-γ up-regulated the expression of BAFF-R in multiple myeloma cells through the NF-κB pathway / 中华微生物学和免疫学杂志

Objective To investigate the action and mechanism of NF-κB pathway in up-regulating B cell-activating factor receptor (BAFF-R) expression in multiple myeloma cells induced by IFN-γ.Methods Activated NF-κB were detected with Western blot, while the expression of BAFF-R were measured with RT-PCR and ELISA, and investigated the effect of BAY11-7082 on transcription of BAFF-R mRNA and translation of protein in multiple myeloma cells stimulated by IFN-γ. Results IFN-γ can induce the degradation of IκB-α in time-dependent and dosage-dependent manner, and up-regulated BAFF-R expression in multiple myeloma cells. BAY11-7082, an NF-κB inhibitor, inhibited not only the transcription of BAFF-R mRNA but also the protein of regulated by IFN-γin dosage-dependent manner. Conclusion NFκB may play an important role in high expression of BAFF-R in multiple myeloma cells induced by IFN-γ.