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.
Autoimmune Diseases/drug therapy* ; B-Cell Activating Factor/therapeutic use* ; B-Lymphocytes ; Humans ; Interleukin-4 ; Lupus Erythematosus, Systemic/drug therapy*

OBJECTIVE: To observe the efficacy of plasma exchange in the treatment of patients with immune thrombocytopenic purpura (ITP), and to analyze the factors influencing the efficacy of plasma exchange in the treatment of ITP. METHODS: The medical records of 39 ITP patients who were treated effectively by plasma exchange in Huai'an First People's Hospital from January 2013 to January 2021 were retrospectively analyzed, and they were set as the effective group. In addition, the medical records of 39 ITP patients who were treated ineffective by plasma exchange during the same period in our hospital were collected, and they were set as the ineffective group. The general data such as sex and age of patients and laboratory indicators on admission were collected and recorded. The possible influencing factors were included, and Logistic regression analysis was used to examine the influencing factors of efficacy of plasma exchange in the treatment of ITP. RESULTS: The serum levels of IL-6, IL-18 and B lymphocyte activating factor (BAFF) on admission in the ineffective group were significantly higher than those in the effective group, and the proportions of Helicobacter pylori (HP) infection and splenomegaly were significantly higher than those in the effective group (P<0.05). There was no statistical significantly difference in sex, age and other data between the two groups (P>0.05). After single factor analysis, multiple regression model was established, which showed that splenomegaly, HP infection and the over expression of serum IL-6, IL-18 and BAFF on admission might be the influencing factors of ineffective treatment of ITP by plasma exchange (OR>1, P<0.05). CONCLUSION The over expression of serum IL-6, IL-18, BAFF, splenomegaly and HP infection on admission may be the influencing factors resulting in the ineffective treatment of plasma exchange in ITP.
B-Cell Activating Factor ; Humans ; Interleukin-18 ; Interleukin-6 ; Plasma Exchange ; Purpura, Thrombocytopenic, Idiopathic/therapy* ; Retrospective Studies ; Splenomegaly

PURPOSE: Despite medical and surgical treatments, some cases of nasal polyps (NP) exhibit recidivism. However, the endotype of refractory chronic rhinosinusitis with NP (CRSwNP) remains unclear. Therefore, the objective of this study was to characterize the immunological profile of refractory CRSwNP. METHODS: The control (n =23), primary NP group (pNP, n =70) and refractory NP group (rNP, n =86) were enrolled in this study. Patients who underwent revision surgeries due to failed maximal medical treatment after primary surgery were defined as the rNP group. A total of 18 inflammatory markers were investigated in nasal tissues using multiplex cytokine assay or enzyme-linked immunosorbent assay. RESULTS: The clinical characteristics of rNP included more extensive disease and worse clinical course after surgery. Additionally, rNP subjects showed higher infection rate (mucopurulence and culture-positive rate), more frequent use of antibiotics and suffered from symptomatic bacterial infection, increased asthma morbidity compared to pNP. Cytokine profile analysis showed that levels of Th17-associated mediators (myeloperoxidase, interleukin (IL)-8, IL-17A and IL-23), B-cell activating factor (BAFF) and Th1 cytokine (interferon-γ) were up-regulated in rNP compared to controls and pNP. Human neutrophil elastase-positive cells were also enhanced in rNP compared with pNP. Upregulation of Th17/Th1mediators and BAFF were observed in rNP, regardless of tissue eosinophilia or asthmatic comorbidity. Interestingly, eosinophilic markers, such as eosinophil cationic protein and C-C motif chemokine ligand 24, were up-regulated in asthmatic rNP compared to pNP and controls. Levels of anti-dsDNA immunoglobulin (Ig) G and IgA were up-regulated in rNP and highest in asthmatic eosinophilic rNP among subtypes of rNP. CONCLUSIONS: Our results suggest that Th17/Th1-associated mediators and BAFF may play a role and be a potential therapeutic target in refractory CRSwNP. Additionally, eosinophilic markers and autoantibodies may contribute to refractoriness in asthmatic rNP.
Anti-Bacterial Agents ; Asthma ; Autoantibodies ; B-Cell Activating Factor ; Bacterial Infections ; Comorbidity ; Enzyme-Linked Immunosorbent Assay ; Eosinophil Cationic Protein ; Eosinophilia ; Eosinophils ; Humans ; Immunoglobulin A ; Immunoglobulins ; Interleukin-17 ; Interleukins ; Nasal Polyps ; Neutrophils ; Sinusitis ; Th17 Cells ; Up-Regulation

<b>OBJECTIVEb>To detect potential mutation of the WAS gene in a Chinese family affected with Wiskott-Aldrich syndrome.

<b>METHODSb>Peripheral blood samples were collected from the proband and his family members. All exons and flanking regions of the WAS gene were subjected to PCR amplification - Sanger sequencing as well as restriction endonuclease analysis. Plasma level of B-cell activating factor (BAFF) was also determined for all family members.

<b>RESULTSb>A hemizygous mutation (c.257G>A) of the WAS gene was identified in all patients from the family, for which the patient's mother was heterozygous. The same mutation was not found among healthy members of the family. Compared with unaffected members, all patients had a higher level of BAFF.

<b>CONCLUSIONb>The c.257G>A mutation of the WAS gene probably underlies the Wiskott-Aldrich syndrome in this family.

B-Cell Activating Factor ; blood ; Child, Preschool ; Heterozygote ; Humans ; Male ; Mutation ; Wiskott-Aldrich Syndrome ; genetics ; Wiskott-Aldrich Syndrome Protein ; genetics

BACKGROUND AND OBJECTIVES: Many kinds of inflammatory cells and cytokines are suggested to be related with pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP), but its mechanism is not yet fully understood. In particular, little is known about the function and role of Interleukin-10 (IL-10) producing regulatory B cells. The aim of this study was to investigate the presence and function of B cells, especially IL-10-producing regulatory B cells, in the nasal polyp (NP) and nasal mucosa. SUBJECTS AND METHOD: Twenty patients with CRSwNP, 10 patients with chronic rhinosinusitis without nasal polyp (CRSsNP) and 10 control subjects were enrolled in this study. NP tissues and uncinate tissues were collected for analysis. Real-time polymerase chain reaction (RT-PCR), immunohistochemistry were performed to measure the expression levels of the selected inflammatory cytokines and inflammation-associated molecules. RESULTS: In the mucosal tissues of CRSsNP patients, the number of IL-10+ B cells was significantly lower than that of NP and control mucosa of CRSwNP patients. The number of IL-10+ B cells was significantly increased in the eosinophilic NP, non-eosinohilic NP, CRSsNP, and control groups. There was a significant positive correlation between the number of IL-10+ B cells and B cell activating factor (BAFF). CONCLUSION: The expression of IL-10+ B cells and BAFF was significantly increased in CRSwNP patients compared to CRSsNP patients and control mucosal tissues, and IL-10+ B cells were more significantly increased in eosinophilic tissues. These results indicate that regulatory B cells are involved in the pathophysiology of eosinophilic NP and that BAFF contributes to the production of regulatory B cells.
B-Cell Activating Factor ; B-Lymphocytes* ; B-Lymphocytes, Regulatory ; Cytokines ; Eosinophils ; Humans ; Immunohistochemistry ; Interleukin-10 ; Methods ; Mucous Membrane ; Nasal Mucosa ; Nasal Polyps ; Real-Time Polymerase Chain Reaction ; Rhinitis ; Sinusitis*

To review B-cell activating factor (BAFF)-antagonist therapy in systemic lupus erythematosus (SLE), literature was searched using the search words and phrases, “BAFF”, “B lymphocyte stimulator (BLyS)”, “a proliferation-inducing ligand (APRIL)”, “B-cell maturation antigen (BCMA)”, “transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)”, “BLyS receptor 3 (BR3)”, “belimumab”, “atacicept”, “blisibimod”, “tabalumab”, and “lupus clinical trial”. In addition, papers from the author's personal library were searched. BAFF-antagonist therapy in SLE has a checkered past, with four late-stage clinical trials meeting their primary endpoints and four failing to do so. Additional late-stage clinical trials are enrolling subjects to address some of the remaining unresolved questions, and novel approaches are proposed to improve results. The BAFF-centric pathway is a proven therapeutic target in SLE. As the only pathway in the past 50+ years to have yielded an United States Food and Drug Administration-approved drug for SLE, it occupies a unique place in the armamentarium of the practicing rheumatologist. The challenges facing clinicians and investigators are how to better tweak the BAFF-centric pathway and improve on the successes realized.
B-Cell Activating Factor* ; B-Lymphocytes* ; Cyclophilins ; Humans ; Lupus Erythematosus, Systemic* ; Lymphocytes ; Research Personnel ; United States

To review B-cell activating factor (BAFF)-antagonist therapy in systemic lupus erythematosus (SLE), literature was searched using the search words and phrases, “BAFF”, “B lymphocyte stimulator (BLyS)”, “a proliferation-inducing ligand (APRIL)”, “B-cell maturation antigen (BCMA)”, “transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI)”, “BLyS receptor 3 (BR3)”, “belimumab”, “atacicept”, “blisibimod”, “tabalumab”, and “lupus clinical trial”. In addition, papers from the author's personal library were searched. BAFF-antagonist therapy in SLE has a checkered past, with four late-stage clinical trials meeting their primary endpoints and four failing to do so. Additional late-stage clinical trials are enrolling subjects to address some of the remaining unresolved questions, and novel approaches are proposed to improve results. The BAFF-centric pathway is a proven therapeutic target in SLE. As the only pathway in the past 50+ years to have yielded an United States Food and Drug Administration-approved drug for SLE, it occupies a unique place in the armamentarium of the practicing rheumatologist. The challenges facing clinicians and investigators are how to better tweak the BAFF-centric pathway and improve on the successes realized.
B-Cell Activating Factor* ; B-Lymphocytes* ; Cyclophilins ; Humans ; Lupus Erythematosus, Systemic* ; Lymphocytes ; Research Personnel ; United States

The effect of hydroxychloroquine (HCQ) on dry eye has not been fully determined. This study aimed to compare the 12-week efficacy of HCQ medication with that of a placebo in the management of dry eye in primary Sjögren's syndrome (pSS). A double-blind, randomized control study was conducted in 39 pSS subjects from May 2011 through August 2013. pSS was diagnosed based on the classification criteria of the American-European Consensus Group. Subjects received 300 mg of HCQ or placebo once daily for 12 weeks and were evaluated at baseline, 6, and 12 weeks, with a re-visit at 16 weeks after drug discontinuance. The fluorescein staining score, Schirmer test score, tear film break-up time (TBUT), and ocular surface disease index (OSDI) were measured, and tears and blood were collected for ESR, IL-6, IL-17, B-cell activating factor (BAFF), and Th17 cell analysis. Color testing was performed and the fundus was examined to monitor HCQ complications. Twenty-six subjects completed the follow-up. The fluorescein staining score and Schirmer test score did not differ significantly. The OSDI improved with medication in the HCQ group but was not significantly different between the groups. TBUT, serum IL-6, ESR, serum and tear BAFF, and the proportion of Th17 cells did not change in either group. HCQ at 300 mg daily for 12 weeks has no apparent clinical benefit for dry eye and systemic inflammation in pSS (ClinicalTrials.gov. NCT01601028).
Aged ; B-Cell Activating Factor/analysis/blood ; Blood Sedimentation ; Double-Blind Method ; Drug Administration Schedule ; Dry Eye Syndromes/complications/*drug therapy ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Hydroxychloroquine/*therapeutic use ; Interleukin-16/analysis/blood ; Interleukin-17/analysis/blood ; Male ; Middle Aged ; Placebo Effect ; Prospective Studies ; Sjogren's Syndrome/*complications/diagnosis ; Th17 Cells/cytology/immunology ; Treatment Outcome

<b>OBJECTIVEb>To study the expression of B-cell activating factor (BAFF) in the serum and cerebrospinal fluid of patients with neuromyelitis optical (NMO).

<b>METHODSb>Clinical data were collected from 44 patients with NMO and 38 patients with multiple sclerosis (MS). Thirty healthy controls and 15 controls with noninflammatory neurological diseases were also recruited. The concentration of BAFF in the serum and cerebrospinal fluid were measured by enzyme-linked immunosorbent assay (ELISA).

<b>RESULTSb>The mean serum BAFF level was 250.2 ± 126.9 pg/ml in NMO patients, 249.6 ± 130.7 pg/ml in MS patients, and 222.9 ± 126.1 pg/ml in the control subjects, showing no significant difference among the 3 groups (P>0.05). The mean BAFF level in the CSF was significantly higher in NMO patients than in MS patients (525.8 ± 230.0 pg/ml vs 298.4 ± 141.9 pg/ml, P<0.05), and higher in MS patients than in the control subjects (141.4 ± 76.2 pg/ml, P<0.05). Both NMO and MS group showed a positive correlation between EDSS scores and CSF BAFF level. But in NMO patients, CSF BAFF level was not associated with AQP4-antibody titer.

<b>CONCLUSIONb>BAFF in the CSF may be a useful biomarker for a differential diagnosis of NMO from MS and has an important value in evaluating the disease severity.

B-Cell Activating Factor ; blood ; cerebrospinal fluid ; Biomarkers ; blood ; cerebrospinal fluid ; Case-Control Studies ; Diagnosis, Differential ; Enzyme-Linked Immunosorbent Assay ; Humans ; Multiple Sclerosis ; blood ; cerebrospinal fluid ; Neuromyelitis Optica ; blood ; cerebrospinal fluid

Skeletal fluorosis is a chronically metabolic bone disease with extensive hyperostosis osteosclerosis caused by long time exposure to fluoride. Skeletal fluorosis brings about a series of abnormal changes of the extremity, such as joint pain, joint stiffness, bone deformity, etc. Differentiation and maturation of osteoblasts were regulated by osteoclasts via Sema4D/Plexin-B1 signaling pathway. Furthermore, the differentiation and maturation of osteoclasts are conducted by osteoblasts via RANKL/RANK/OPG pathway. Both of these processes form a feedback circuit which is a key link in skeletal fluorosis. In this study, an osteoblast-osteoclast co-culture model in vitro was developed to illustrate the mechanism of skeletal fluorosis. With the increase of fluoride concentration, the expression level of Sema4D was decreased and TGF-β1 was increased continuously. OPG/RANKL mRNA level, however, increased gradually. On the basis of that, the inhibition of Sema4D/Plexin-B1/RhoA/ROCK signaling pathway caused by fluoride promoted the level of TGF-β1 and activated the proliferation of osteoblasts. In addition, osteroprotegerin (OPG) secreted by osteoblasts was up-regulated by fluoride. The competitive combination of OPG and RANKL was strengthened and the combination of RANKL and RANK was hindered. And then the differentiation and maturation of osteoclasts were inhibited, and bone absorption was weakened, leading to skeletal fluorosis.
Animals ; Antigens, CD ; genetics ; metabolism ; Cell Proliferation ; drug effects ; Feedback, Physiological ; Fetus ; Fluorides ; pharmacology ; GTPase-Activating Proteins ; genetics ; metabolism ; Gene Expression Regulation, Developmental ; Osteoblasts ; drug effects ; metabolism ; pathology ; Osteoclasts ; drug effects ; metabolism ; pathology ; Osteogenesis ; drug effects ; genetics ; Osteoprotegerin ; genetics ; metabolism ; RANK Ligand ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Receptor Activator of Nuclear Factor-kappa B ; genetics ; metabolism ; Receptors, Cell Surface ; genetics ; metabolism ; Semaphorins ; genetics ; metabolism ; Signal Transduction ; Transforming Growth Factor beta1 ; genetics ; metabolism ; rho-Associated Kinases ; genetics ; metabolism ; rhoA GTP-Binding Protein ; genetics ; metabolism