B-cell Activating Factor Of TNF Family Research Articles

BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis.

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19+ B cells, CD19+CD27+ B cells, CD19+CD20+CD27+ B cells, and CD19+CD20-CD27+ B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19+BAFFR+ B cells, CD19+ BCMA+ B cells, and CD19+ TACI+ B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.

Heterozygous signal transducer and activator of transcription 3 mutations in hyper-IgE syndrome result in altered B-cell maturation

Heterozygous signal transducer and activator of transcription 3 mutations in hyper-IgE syndrome result in altered B-cell maturation

Serum Levels of B-Cell Activating Factor of TNF Family (BAFF) as a Useful Indicator for the Activity of Graves' Disease

Background : Graves’ disease (GD) is a thyroid-specific autoimmune disorder. Both B-cell activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are cytokines which share a role for regulating survival and proliferation of B lymphocytes. Elevated level of these cytokines in circulation was observed in several types of autoimmune diseases. However, there were no reports focusing on the potential relationship between BAFF and the activity of GD. To explore the pathophysiologic role of BAFF and APRIL in GD, we investigated serum levels of BAFF and APRIL in patients with GD. Methods : We enrolled twenty three patients newly diagnosed as GD and twenty healthy donors as controls. We measured serum levels of BAFF and APRIL in patients and controls by ELISA. Results : Serum level of BAFF was significantly elevated in patients with GD compared to controls (1329 + 435 pg/mL vs. 983 + 308 pg/mL, P Conclusions : Findings in the present study offer a novel opportunity to evaluate GD. doi:10.4021/jem16w

Short citrullinated epitope of filaggrin is recognised by sera as well as antibodies produced in vitro by B cells of rheumatoid arthritis patients

Background and objectivesAutoantibodies in about 70% of rheumatoid arthritis (RA) patients recognising citrullinated proteins (ACPA) are cross-reactive with citrullinated filaggrin epitopes. Although filaggrin is an epithelial protein and is not...

Serum Levels of B-Cell Activating Factor of TNF Family (BAFF) as a Useful Indicator for the Activity of Graves’ Disease

Background : Graves’ disease (GD) is a thyroid-specific autoimmune disorder. Both B-cell activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL) are cytokines which share a role for regulating survival and proliferation of B lymphocytes. Elevated level of these cytokines in circulation was observed in several types of autoimmune diseases. However, there were no reports focusing on the potential relationship between BAFF and the activity of GD. To explore the pathophysiologic role of BAFF and APRIL in GD, we investigated serum levels of BAFF and APRIL in patients with GD. Methods : We enrolled twenty three patients newly diagnosed as GD and twenty healthy donors as controls. We measured serum levels of BAFF and APRIL in patients and controls by ELISA. Results : Serum level of BAFF was significantly elevated in patients with GD compared to controls (1329 + 435 pg/mL vs. 983 + 308 pg/mL, P < 0.01). Notably, serum BAFF level was significantly correlated with free-T3 to free-T4 ratio (FT3/FT4), a useful indicator for the disease activity of GD. Conclusions : Findings in the present study offer a novel opportunity to evaluate GD. J Endocrinol Metab. 2011;1(2):73-78 doi: https://doi.org/10.4021/jem16w

Airway Epithelial Cells Produce B Cell-Activating Factor of TNF Family by an IFN-β-Dependent Mechanism

Activation of B cells in the airways is now believed to be of great importance in immunity to pathogens, and it participates in the pathogenesis of airway diseases. However, little is known about the mechanisms of local activation of B cells in airway mucosa. We investigated the expression of members of the B cell-activating TNF superfamily (B cell-activating factor of TNF family (BAFF) and a proliferation-inducing ligand (APRIL)) in resting and TLR ligand-treated BEAS-2B cells and primary human bronchial epithelial cells (PBEC). In unstimulated cells, expression of BAFF and APRIL was minimal. However, BAFF mRNA was significantly up-regulated by TLR3 ligand (dsRNA), but not by other TLR ligands, in both BEAS-2B cells (376-fold) and PBEC (224-fold). APRIL mRNA was up-regulated by dsRNA in PBEC (7-fold), but not in BEAS-2B cells. Membrane-bound BAFF protein was detectable after stimulation with dsRNA. Soluble BAFF protein was also induced by dsRNA (> 200 pg/ml). The biological activity of the epithelial cell-produced BAFF was verified using a B cell survival assay. BAFF was also strongly induced by IFN-beta, a cytokine induced by dsRNA. Induction of BAFF by dsRNA was dependent upon protein synthesis and IFN-alphabeta receptor-JAK-STAT signaling, as indicated by studies with cycloheximide, the JAK inhibitor I, and small interfering RNA against STAT1 and IFN-alphabeta receptor 2. These results suggest that BAFF is induced by dsRNA in airway epithelial cells and that the response results via an autocrine pathway involving IFN-beta. The production of BAFF and APRIL by epithelial cells may contribute to local accumulation, activation, class switch recombination, and Ig synthesis by B cells in the airways.