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Abstract Background Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy. Methods We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits. Results We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group. Conclusion Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process.

B cells are critically important for the pathogenesis of IgA nephropathy (IgAN). The present study aimed to investigate the abundance of B cell activating factor (BAFF), which belongs to the tumor necrosis factor superfamily, in the peripheral blood of patients with IgAN. The different forms of BAFF in peripheral blood and its association with clinical features and immunological factors were analyzed. mRNA levels of BAFF and other associated genes in the peripheral blood mononuclear cells (PBMCs) of patients with IgAN and controls were analyzed by quantitative polymerase chain reaction. Cellular BAFF proteins in PBMCs and plasma soluble BAFF proteins were measured by western blot analysis and ELISA, respectively. PBMCs from patients were stimulated with Streptococcus pyogenes (S. pyogenes) ex vivo for the BAFF secretion assay. The data demonstrated that, although mRNA levels of BAFF in PBMC were not significantly increased in patients with IgAN, they were positively associated with those of a proliferation inducing ligand (APRIL), Toll-like receptor (TLR)2, TLR4 and TLR7. The cellular BAFF protein in PBMCs was not upregulated. Plasma BAFF protein levels in patients with IgAN (n=76) were significantly decreased compared with controls. However, plasma BAFF levels were positively associated with serum creatinine, proteinuria, uric acid and group A Streptococcus infection index in patients with IgAN. In patients with IgAN, plasma BAFF concentrations were markedly higher in those with more severe renal tubular atrophy/interstitial fibrosis and global glomerulosclerosis. Furthermore, BAFF production in PBMCs of patients with IgAN was increased following S. pyogenes stimulation ex vivo. In conclusion, plasma BAFF levels in patients with IgAN were associated with renal function and disease activity. S. pyogenes infection was closely associated with BAFF production in patients with IgAN. [ABSTRACT FROM AUTHOR]

IgA nephropathy (IgAN) has become the most common form of primary glomerular disease worldwide. So far, it is still not very clear about the exact pathogenesis of IgAN, thus has no specific therapy. Generally mesangial deposition of IgA, especially polymeric IgA1 (pIgA1), suggests to be the initiating event in the pathogenesis of IgAN. In addition to decreased IgA clearance, IgA over production may also participate in the pathogenesis of IgAN. IgA class switching recombination (CSR) played key role during the process of IgA production. Stimulated with hemolytic streptococcus, tonsillar mononuclear cells (TMCs) of patients with IgAN presented with increased levels of Ia-Ca and activation-induced cytidine deaminase (AID), which are significant for IgA CSR. Human B cells and plasmacytoid dendritic cells express Toll-like receptor (TLR)-9, whose natural ligands are unmethylated cytosine-guanine dinucleotide (CpG) motifs characteristic of bacterial DNA (CpG-DNA). Unmethylated deoxycytidylic-deoxyguanosine oligodeoxynucleotide (CpG-ODN) is able to mimic the immunostimulatory activity of microbial DNA. Study found a significant increase in B cell activation factor (BAFF) production when tonsillar mononuclear cells stimulated with CpG-ODN in patients with IgAN. BAFF can induce germline Cα gene expression, AID expression, and IgA class switching in a CD40-independent manner. Therefore, it could be hypothesized that in IgAN there may exist TLR9-BAFF-IgA CSR axis, which induces excessive IgA production. If the hypothesis is correct, it could be of great significance for pathogenesis of IgAN elucidate and IgAN treatment. [ABSTRACT FROM AUTHOR]

Background: Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy.Methods: We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits.Results: We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group.Conclusion: Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process. [ABSTRACT FROM AUTHOR]

We describe a bispecific dual-antagonist antibody against human B cell activating factor (BAFF) and interleukin 17A (IL-17). An anti-IL-17 single-chain variable fragment (scFv) derived from ixekizumab (Taltz®) was fused via a glycine-rich linker to anti-BAFF tabalumab. The IgG-scFv bound both BAFF and IL-17 simultaneously with identical stoichiometry as the parental mAbs. Stability studies of the initial IgG-scFv revealed chemical degradation and aggregation not observed in either parental antibody. The anti-IL-17 scFv showed a high melting temperature ( Tm ) by differential scanning calorimetry (73.1°C), but also concentration-dependent, initially reversible, protein self-association. To engineer scFv stability, three parallel approaches were taken: labile complementary-determining region (CDR) residues were replaced by stable, affinity-neutral amino acids, CDR charge distribution was balanced, and a H44-L100 interface disulfide bond was introduced. The Tm of the disulfide-stabilized scFv was largely unperturbed, yet it remained monodispersed at high protein concentration. Fluorescent dye binding titrations indicated reduced solvent exposure of hydrophobic residues and decreased proteolytic susceptibility was observed, both indicative of enhanced conformational stability. Superimposition of the H44-L100 scFv (PDB id: 6NOU) and ixekizumab antigen-binding fragment (PDB id: 6NOV) crystal structures revealed nearly identical orientation of the frameworks and CDR loops. The stabilized bispecific molecule LY3090106 (tibulizumab) potently antagonized both BAFF and IL-17 in cell-based and in vivo mouse models. In cynomolgus monkey, it suppressed B cell development and survival and remained functionally intact in circulation, with a prolonged half-life. In summary, we engineered a potent bispecific antibody targeting two key cytokines involved in human autoimmunity amenable to clinical development.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is one of the common diseases. Involving the nasal passages and nasal passages, it may affect 10% of the global population. Surgical intervention is usually required. Its pathogenesis is a multielement and multistep complex process. Current multi-factor hypothesisplays a dominant role in the etiology of nasal polyps (NP). Infectious factors always play an important role in the pathogenesis of CRSwNP. The lesions of nasal polyp have different inflammatory cell infiltration and can be divided into two types in immunophenotpe: the first is characterized by Th2 cell reaction and marked eosinophil infiltration,and the second is Th1/Th17 cell response and non-eosinophil infiltration are characteristic.NP, which is mainly infiltrated by neutrophils, is more and more common in China. B cell activation factor (BAFF) is a major inflammatory factor related to the regulation of B cell activation.Recent experiments have shown that BAFF is also high in nasal polyps.In this paper, the effects and interactions of BAFF and eosinophils and neutrophils in CRSwNP were reviewed., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Adipose tissue functions as a key endocrine organ by releasing multiple bioactive substances, and plays a key role in the integration of systemic metabolism. We have previously shown that B cell activating factor is produced mainly in visceral adipose tissue and affects insulin sensitivity in obese individuals. In this study, we identified the signals that lead to production of B cell activating factor in adipocytes. 3T3-L1 and C3H/10T 1/2-clone 8 cells showed increased B cell activating factor expression upon exposure to hydrogen peroxide, and these changes were inhibited by treatment with the antioxidant N-acetyl-cysteine. B cell activating factor levels in both serum and visceral adipose tissue were increased in high fat diet-fed mice, and these increases were correlated with oxidative stress. In addition, serum BAFF levels in high fat diet-fed mice were reduced by N-acetyl-cysteine treatment. We also found that oxidative stress-induced B cell activating factor expression in adipocytes was regulated by NF-κB activation. These data indicate that control of the redox state in visceral adipose tissue is a potentially useful target for treating metabolic syndromes through regulation of adipokine production.