RESUMO
Immune dysregulation is an important aspect of schizophrenia (SZ) and bipolar disorders (BD) pathophysiology, including not only inflammatory but also autoimmune process reflective of abnormal humoral immune responses. Given that B cell-activating factor (BAFF) is an integral aspect of B lymphocyte regulation, the current study investigated BAFF in SZ and BD. 255 SZ patients, 407 BD patients and 185 healthy controls (HC) were investigated across three aspects of soluble BAFF (sBAFF) by (i) comparing sBAFF circulatory levels across SZ, BD and HC, (ii) determining potential correlations between the circulating levels of sBAFF and the genotype distribution of a functionally relevant polymorphism, namely the TNFSF13B 3'UTR insertion-deletion polymorphism (GCTGT>A), (iii) analyzing relationships between both sBAFF levels and 3'UTR insertion-deletion genotypes and disease risk, patients clinical characteristics and circulating levels of potent inflammatory molecules. In addition, in subsets of patients, we also searched for possible correlations between sBAFF levels and stigma of past infectious events as well as positivity for circulating systemic autoantibodies or those directed against central nervous system (CNS) structures. Studying blood derived serum and DNA, weobserved that circulating sBAFF levels were significantly higher in SZ and BD patients, versus HC (p = 5.3*10-10and p = 4.4*10-09). Patients experiencing acute episodes, versus stable patients, in between acute episodes, exhibited higher sBAFF levels (p = 0.017).In SZ patients, positive correlations were observed between elevated sBAFF levels and: (i) elevated positive psychotic symptoms (PANSS pos), (ii) history of childhood trauma (physical abuse), and (iii) low scores on global functioning (GAF) (p = 0.024, p = 0.024, and p = 0.041).We also found that the distribution of the BAFF Ins/Del genotypes was significantly correlated with circulating sBAFF levels in SZ and BD patients (p = 0.0004). Elevated sBAFF levels were also correlated with increased levels of pro-inflammatory markers in both SZ and BD cohorts (p < 0.001). Regarding infectious stigma, only patients seropositive, versus seronegative, for herpes simplex virus (HSV)1 immunoglobulin (Ig)G antibodies exhibited a significant association with high sBAFF levels (p = 0.013). In contrast, positivity for systemic or CNS autoantibodies was significantly associated with reduced sBAFF levels, compared to patients without autoantibodies (p = 0.0017). Overall, our findings indicate that BAFF may be a promising trans-nosographic biomarker of inflammation that is likely to offer predictive, diagnostic, and prognostic tools for the management of SZ and BD. The results therefore have practicable clinical utility given the availability of immunotherapeutic treatment options including targeted monoclonal antibodies against BAFF.
RESUMO
Although rituximab is not specifically approved for the treatment of warm autoimmune hemolytic anemia (WAIHA), the First International Consensus Group recommends considering its use as part of the initial therapy for patients with severe disease and as a second-line therapy for primary WAIHA. Some patients do not respond to rituximab, and relapses are common. These relapses are associated with elevated B-cell-activating factor (BAFF) levels and the presence of quiescent long-lived plasma cells (LLPCs) in the spleen. A new group of immunomodulatory drugs, B-cell-activating factor inhibitors (BAFF-i), demonstrated efficacy in multiple autoimmune diseases and have the potential to improve WAIHA treatment outcomes by targeting B-cells and LLPCs. This article reviews the role of BAFF in autoimmune disorders and the currently available literature on the use of BAFF-directed therapies in various immunologic disorders, including WAIHA. Collectively, the clinical data thus far shows robust potential for targeting BAFF in WAIHA therapy.
Assuntos
Anticorpos Monoclonais Humanizados , Dermatomiosite , Humanos , Dermatomiosite/tratamento farmacológico , Dermatomiosite/complicações , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Masculino , Criança , Adolescente , Imunossupressores/uso terapêutico , Índice de Gravidade de Doença , Adulto , Resultado do Tratamento , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a potentially life-threatening complication among Multiple Sclerosis (MS) patients under natalizumab treatment, with serum anti-JCV antibody titers being used for stratification risk. Given the critical role of interferon (IFN)/B-cell activating factor (BAFF) axis in humoral immune responses against viruses, we explored whether it is involved in the generation of serum anti-JCV antibodies among these patients. METHODS: 162 consecutive patients with relapsing-remitting MS under natalizumab treatment were included. Serum anti-JCV antibodies were measured at baseline, as well as 12 and 24 months after treatment initiation. Type I and II IFN-inducible genes and BAFF expression were quantitated in peripheral blood by qRT-PCR. Moreover, BAFF rs9514828, rs1041569, and rs9514827 gene variants were assessed by RFLP-PCR. RESULTS: While type I and II IFN inducible gene expression were not associated with anti-JCV serum titers, the latter were significantly correlated with BAFF gene expression. Of interest, the TTT haplotype of the studied BAFF variants was more frequently detected in male, but not female anti-JCV (+) MS patients compared to anti-JCV (-) counterparts at baseline, as well as at 12 months and 24 months of natalizumab treatment. Measures of clinical validity/utility for the BAFF TTT haplotype showed 88% specificity, 45%, positive predictive value, and sensitivity of 70% for the discrimination of anti-JCV (+) male MS patients after 24 months of treatment. CONCLUSIONS: Our study suggests an implication of the BAFF axis in the production of serum anti-JCV antibodies. Additionally, the BAFF TTT haplotype derived from the rs9514828, rs1041569, and rs9514827 variants may represent a novel risk factor for anti-JCV seropositivity and indirectly for PML development among male MS patients treated with natalizumab.
Assuntos
Fator Ativador de Células B , Fatores Imunológicos , Vírus JC , Leucoencefalopatia Multifocal Progressiva , Natalizumab , Humanos , Natalizumab/uso terapêutico , Fator Ativador de Células B/sangue , Fator Ativador de Células B/genética , Masculino , Leucoencefalopatia Multifocal Progressiva/sangue , Leucoencefalopatia Multifocal Progressiva/genética , Adulto , Feminino , Fatores Imunológicos/uso terapêutico , Vírus JC/imunologia , Vírus JC/genética , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/imunologia , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background: Refractory generalized myasthenia gravis (GMG) remains a substantial therapeutic challenge. Telitacicept, a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein, holds promise for interrupting the immunopathology of this condition. Objectives: This study retrospectively assessed the effectiveness and safety of telitacicept in patients with refractory GMG. Design: A single-center retrospective study. Methods: Patients with refractory GMG receiving telitacicept (160 mg/week or biweekly) from January to September in 2023 were included. We assessed effectiveness using Myasthenia Gravis Foundation of America post-intervention status (MGFA-PIS), myasthenia gravis treatment status and intensity (MGSTI), quantitative myasthenia gravis (QMG), and MG-activity of daily living (ADL) scores, alongside reductions in prednisone dosage at 3- and 6-month intervals. Safety profiles were also evaluated. Results: Sixteen patients with MGFA class II-V refractory GMG were included, with eight females and eight males. All patients were followed up for at least 3 months, and 11 patients reached 6 months follow-up. At the 3-month evaluation, 75% (12/16) demonstrated clinical improvement with MGFA-PIS. One patient achieved pharmacological remission, two attained minimal manifestation status, and nine showed functional improvement; three remained unchanged, and one deteriorated. By the 6-month visit, 90.1% (10/11) sustained significant symptomatic improvement. MGSTI scores and prednisone dosages significantly reduced at both follow-ups (p < 0.05). MG-ADL and QMG scores showed marked improvement at 6 months (p < 0.05). The treatment was well tolerated, with no severe adverse events such as allergy or infection reported. Conclusion: Our exploratory investigation suggests that telitacicept is a feasible and well-tolerated add-on therapy for refractory GMG, offering valuable clinical evidence for this novel treatment option.
RESUMO
B-cell activating factor (BAFF), a critical regulator of B cells, is involved in various autoimmune diseases. Inflammatory bowel disease (IBD) is a group of chronic and recurrent intestinal inflammatory disorders with unclear etiology, and its global incidence has been increasing in recent years. Abnormal immune responses triggered by multiple factors are closely related to the pathogenesis of IBD. Previous studies have confirmed the association of B-cell abnormal activation and increased production of autoantibodies with the development of ulcerative colitis. However, the involvement of BAFF in the mechanisms of IBD remains unclear. This review summarizes the potential role of BAFF in the pathogenesis of IBD and provides an overview of targeted therapies on BAFF in IBD, aiming to contribute insights for targeted treatments of IBD.
Assuntos
Fator Ativador de Células B , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Fator Ativador de Células B/metabolismo , Linfócitos B , Colite Ulcerativa/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologiaRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is a prevalent condition with an unclear pathogenesis. B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are potential key players in GDM. PARTICIPANTS, MATERIALS, AND METHODS: In a longitudinal observational study, we monitored women from the first trimester through 24-28 weeks of gestation, focusing on the development of GDM. Serum levels of BAFF and APRIL, as well as their mRNA expression, were evaluated in both the first and third trimesters. Furthermore, we assessed cytokines, adipokines, and placental hormones in the serum. RESULTS: In the first trimester, participants who later developed GDM exhibited elevated serum BAFF and reduced serum APRIL levels, although the mRNA expression of these molecules was similar to controls. Serum BAFF exhibited significant positive correlations with metabolic markers and placental hormones. Conversely, serum APRIL was negatively correlated with insulin resistance and inflammatory markers but positively correlated with adiponectin. In the early third trimester, GDM participants continued to display higher serum BAFF levels and lower serum APRIL levels than controls. There was no significant difference in mRNA expression of BAFF between GDM and control groups. Conversely, APRIL mRNA expression was significantly lower in the GDM group. The predictive potential of first-trimester BAFF and APRIL levels for future GDM development was explored, with both molecules demonstrating strong predictive capability. DISCUSSION AND CONCLUSION: This study suggests that elevated serum BAFF and reduced serum APRIL levels during pregnancy may be associated with the development of GDM. These biomarkers can serve as potential early predictors for GDM.
Assuntos
Fator Ativador de Células B , Biomarcadores , Diabetes Gestacional , Primeiro Trimestre da Gravidez , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Humanos , Fator Ativador de Células B/sangue , Feminino , Gravidez , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adulto , Primeiro Trimestre da Gravidez/sangue , Biomarcadores/sangue , Estudos Longitudinais , Prognóstico , Seguimentos , Estudos de Casos e ControlesRESUMO
BACKGROUND: Rapid progressive interstitial lung disease (RP-ILD) is the leading cause of anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis (anti-MDA5+DM) related death. Elevated serum B-cell activating factor (BAFF) levels have been implicated in connective tissue diseases associated ILD. Here, we evaluate whether BAFF could be a prognostic biomarker for predicting RP-ILD in anti-MDA5+DM patients. METHODS: Serums were collected from 39 patients with anti-MDA5+DM (20 with RP-ILD and 19 with non-RP-ILD), 20 antisynthase syndrome (ASS) patients and 20 healthy controls (HC). BAFF concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: Serum BAFF level was higher in anti-MDA5+DM patients than those in ASS patients and HC (3882.32 ± 1880.09 vs. 2540.89 ± 1403.04 and 2486.28 ± 767.97 pg/mL, p = 0.0056 and 0.0038, respectively). Within anti-MDA5+DM groups, RP-ILD patients exhibited higher BAFF concentration than non-RP-ILD group (4549.78 ± 1839.97 vs. 3297.28 ± 1794.69 pg/mL, p = 0.04). The BAFF concentration was positively correlated with levels of C-reactive protein (CRP), dehydrogenase (LDH) and cytokeratin (CK) in anti-MDA5+DM patients (r = 0.350, p = 0.035; r = 0.393, p = 0.016; r = 0.518, p = 0.001; respectively). The best cut-off value of BAFF concentration was 2971.5 pg/mL by ROC curve (AUC area = 0.690, p = 0.045) and BAFF > 2971.5 pg/mL was an independent risk factor for RP-ILD using multivariate analysis (OR = 9.389, 95% CI = 1.609-54.769; p = 0.013). CONCLUSIONS: Serum BAFF could be a useful prognostic biomarker for early detecting RP-ILD risk in anti-MDA5+DM patients.
Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Humanos , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Helicase IFIH1 Induzida por Interferon , Autoanticorpos , Biomarcadores , Prognóstico , Estudos Retrospectivos , Progressão da DoençaRESUMO
Visceral leishmaniasis (VL) is an infectious disease caused by parasitic protozoa of the genus Leishmania and manifests clinical symptoms such as splenomegaly, hepatomegaly, anemia, and fever. It has previously been shown that B-cell-activating factor (BAFF) is involved in splenomegaly during VL. Although BAFF is known to be expressed by a variety of cells, the mechanism of elevated BAFF expression in VL is not clear. In this study, we aimed to identify BAFF-producing cells in the spleens of mice infected with Leishmania donovani. Splenocytes of L. donovani-infected mice showed elevated BAFF expression compared to that of naive mice. In the infected spleen, the number of both CD11b+ and F4/80+ cells increased, and the major BAFF-producing cells were CD11b+ cells, which did not serve as host cells of Leishmania. Immunohistochemical/immunofluorescent staining of spleens of infected mice revealed that the increased CD11b+ cells were primarily MRP14+ mononuclear cells. Together, these results suggest the increased BAFF expression in the spleen of L. donovani-infected mice involves a recruitment of inflammatory macrophages distinct from host macrophages for the parasites.
RESUMO
Immune thrombocytopenia (ITP) is an autoimmune-driven disease characterized by increased destruction and impaired platelet production resulting in an enhanced risk of bleeding. Immunosuppressant agents are the most common treatment strategies for ITP. Despite their efficacy, these medications often cause unpredictable side effects. Recent investigations revealed that patients with ITP exhibit elevated B-cell activating factor (BAFF) levels in both their spleens and serum. Belimumab, a BAFF inhibitor, illustrated a promising therapeutic avenue for managing ITP by interfering with BAFF activity and long-lived plasma cell production. Both clinical and experimental studies have yielded positive outcomes when combining rituximab with an anti-BAFF monoclonal antibody in treating ITP. In addition, ianalumab, a monoclonal antibody with a dual mechanism that targets BAFF-R and deletes peripheral BAFF-R+ B cells, is currently being used for ITP treatment [NCT05885555]. The upcoming results from novel BAFF inhibitors, such as ianalumab, could offer clinicians an additional therapeutic option for treating ITP.
Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Fator Ativador de Células B , Interleucina-4 , Anticorpos Monoclonais/uso terapêuticoRESUMO
OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a form of SLE associated with severe NP syndromes causing mortality and morbidity. Respecting the fundamental of BAFF in NPSLE pathophysiology, we investigated its clinical value. METHODS: Totally 105 NPSLE and 101 SLE cases without NPSLE (non-NPSLE, control) were included. Serum BAFF/TNF-α/IL-6/IL-10 levels were measured using ELISA kits. T lymphocytes were detected by flow cytometry. The independent influencing factors for NPSLE, and the auxiliary diagnostic efficacy and the ability of BAFF levels to predict adverse prognosis of NPSLE patients were analyzed by multiple factor logistic regression, and ROC curve and survival curve. RESULTS: In NPSLE patients, serum BAFF level was increased and positively correlated with SLEDAI-2k, serum proinflammatory cytokines, while negatively correlated with CD4+T/CD8+T cells, and anti-inflammatory cytokine. High serum BAFF protein level was associated with a higher risk of developing NPSLE. The AUC of serum BAFF > 301.7 assisting in NPSLE diagnosis was 0.8196. Furthermore, high levels of serum BAFF were associated with a higher risk of adverse outcomes in NPSLE patients. . CONCLUSION: Serum BAFF level in NPSLE patients was correlated with lymphocytes and high serum BAFF protein level could assist in diagnosis and to predict adverse outcomes in NPSLE patients.
Assuntos
Fator Ativador de Células B , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Humanos , Fator Ativador de Células B/sangue , Feminino , Masculino , Vasculite Associada ao Lúpus do Sistema Nervoso Central/imunologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/sangue , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Adulto , Pessoa de Meia-Idade , Biomarcadores/sangue , Prognóstico , Citocinas/sangue , Inflamação/sangue , Inflamação/imunologia , Inflamação/diagnóstico , Adulto JovemRESUMO
Objectives: This study investigated the correlation between serum and urinary B cell-activating factor (BAFF) levels and systemic lupus erythematosus (SLE) disease activity. Patients and methods: This case-control study was conducted with 87 participants between December 2020 and September 2021. Sixty-two SLE patients who fulfilled the eligibility criteria were enrolled. SLE patients were categorized into active (n=34) and inactive (n=28) groups based on their Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores. The control group consisted of 25 healthy subjects. Serum and urine samples were collected for the measurement of BAFF levels. Finally, the relationship between these variables and SLE disease activity was investigated. Results: The mean age of active (SLEDAI-2K >4) and inactive (SLEDAI-2K ≤4) SLE patients and healthy individuals were 32.8±7.8, 32.5±6.8, and 31.7±7.8 years, respectively (p=0.62). The median serum BAFF (s-BAFF) and urinary BAFF (u-BAFF) in active lupus patients (10.4 [2.3] ng/mL and 8.2 [3.7] ng/mL, respectively) were significantly higher than in inactive lupus patients (6 (7.1) ng/mL and 1.7 (4.7) ng/mL, respectively; p<0.001) and the control group (3 (3.7) ng/mL and 1.6 (2.2) ng/mL, respectively; p<0.001). However, s-BAFF (p=0.07) and u-BAFF (p=0.43) did not significantly differ between the inactive group and the control group. A significant positive correlation was observed between s-BAFF (r=0.41 and p=0.001) and u-BAFF (r=0.78 and p<0.001) levels and the SLEDAI-2K score. Conclusion: There is a significant positive correlation between serum and urinary BAFF levels and SLE disease activity. Furthermore, significantly higher levels of s-BAFF and u-BAFF have been observed in patients with active lupus compared to inactive and healthy subjects, indicating a possible role for BAFF in the pathogenesis of SLE disease activity.
RESUMO
BACKGROUND: Host-modulating therapy is a possible treatment for individuals that respond poorly to conventional periodontal therapy. B cells, abundant in periodontitis lesions, require the cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) for survival and maturation. Although mRNA levels of BAFF and APRIL are increased in tissue from periodontitis lesions, it is unknown if periodontal resident cells express BAFF and/or APRIL during periodontal inflammation. In this study, we aim to analyze the expression of BAFF and APRIL in human gingival fibroblasts after stimulation with proinflammatory cytokines. Furthermore, we perform protein analysis in tissues and serum from periodontitis patients and healthy controls. METHODS: Human gingival fibroblasts were cultured and stimulated with the proinflammatory cytokines' tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). The mRNA expression of BAFF and APRIL was analyzed by real-time quantitative polymerase chain reaction (qPCR), and the protein was detected in tissue sections using immune staining. Serum levels of BAFF were analyzed with enzyme-linked immunosorbent assay (ELISA). RESULTS: In gingival fibroblasts, TNF-α upregulated BAFF mRNA, but APRIL was unaffected. IL-1ß affected neither BAFF nor APRIL expression. BAFF protein was detected in the oral epithelium and in cells of the underlying connective tissue in periodontitis tissue, and BAFF protein was increased in the serum of periodontitis patients. CONCLUSION: Periodontal resident cells express BAFF during periodontal inflammation and participate in providing a favorable milieu for the survival and action of B cells.
RESUMO
OBJECTIVE: B-cell activating factor (BAFF) is a key regulator of primary Sjögren's syndrome (pSS), which is characterized by B-lymphocyte hyperactivity. BAFF, also known as tumor necrosis factor ligand superfamily member 13B, is encoded by TNFSF13B. This study aimed to explore the possible relationships between five single-nucleotide polymorphisms (SNPs) of TNFSF13B (rs9514827, rs1041569, rs9514828, rs1224141, and rs12583006) and pSS susceptibility. METHODS: We searched the following databases for articles on TNFSF13B polymorphism and pSS published up to January 2023: PubMed, Cochrane, Elsevier, Web of Science, CNKI, CQVIP, and WanFang. The odds ratios (with 95% confidence intervals) of genotypes and SNP alleles of TNFSF13B were investigated in patients with pSS to determine their relationships with pSS. RESULTS: This meta-analysis employing the fixed-effect model comprised three studies of pSS patients and randomly selected healthy controls (HCs), revealing statistically significant relationships between pSS susceptibility and two SNPs: rs1041569 and rs12583006. Because rs1041569 was not in Hardy-Weinberg equilibrium in the HC group, it was eliminated from the analysis. CONCLUSIONS: Polymorphisms in the BAFF (TNFSF13B) gene were related to vulnerability to pSS among pSS patients and HCs alike. The SNP rs12583006 was significantly related to pSS susceptibility in pSS patients.
Assuntos
Fator Ativador de Células B , Síndrome de Sjogren , Humanos , Fator Ativador de Células B/genética , Síndrome de Sjogren/genética , Genótipo , Polimorfismo de Nucleotídeo Único , AlelosRESUMO
Although B cells and B cell activating factor (BAFF) have been previously implicated in MS pathogenesis, data regarding the genetic influence of BAFF polymorphisms on MS susceptibility are limited. Here we aim to explore whether BAFF polymorphisms could contribute to MS susceptibility. 156 RRMS patients fulfilling the revised McDonald criteria for MS diagnosis and 220 HCs were enrolled. Clinical, laboratory, and imaging characteristics were recorded. BAFF rs9514827, rs1041569, and rs9514828 polymorphisms were assessed by RFLP-PCR in DNA samples extracted from whole peripheral blood. The BAFF rs1041569 TT genotype along with the CTT and TTC haplotypes were associated with significantly increased risk for MS development in female MS patients compared to healthy female counterparts. These findings were not confirmed in males. The rs1041569 BAFF variant together with the CTT and TTC BAFF haplotypes derived from the BAFF rs9514827, rs1041569, and rs9514828 polymorphisms may represent novel genetic contributors to the development of MS in females.
Assuntos
Predisposição Genética para Doença , Esclerose Múltipla , Feminino , Humanos , Masculino , Fator Ativador de Células B/genética , Frequência do Gene , Genótipo , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVES: To determine the allelic frequencies and effects of genotypic variations in cytokine gene polymorphisms in a Saudi Arabian population. METHODS: This cross-sectional study involved 41 patients with Primary Sjögren's syndrome (pSS) and 71 healthy controls between October 2018 and May 2019. Single nucleotide polymorphisms genotyping was performed using the SEQUENOM MassARRAY® System, targeting nine polymorphisms in different cytokine genes. Chi-square tests were used to compare the patients and controls. RESULTS: The interleukin-1 beta (IL-1ß) rs1143627 CT (control, 52.7%; patients, 21.2%) and TT + CT (p= 0.003; p=0.033) genotypes were less frequent in patients with pSS than in healthy controls. The C allele in rs10488631 in the interferon regulatory factor 5 (IRF5) gene and the A allele in rs12583006 in the B-cell activating factor (BAFF) gene were associated with an increased risk of pSS development in the patient group. CONCLUSION: The CT genotype at -31 (rs1143627) in the IL-1ß gene was not associated with a high risk of pSS development in the Saudi population, in contrast to what has been verified in other ethnicities. However, the C allele in rs10488631 in IRF-5 and the A allele in rs12583006 in BAFF were associated.
Assuntos
Polimorfismo de Nucleotídeo Único , Síndrome de Sjogren , Humanos , Estudos Transversais , Arábia Saudita , Síndrome de Sjogren/genética , Citocinas/genéticaRESUMO
OBJECTIVE: In pregnancies complicated by maternal obesity and diabetes, a disruption in inflammatory mediators occurs, resulting in endothelial microvascular dysfunction, oxidative stress, tissue damage, and maternal and feto-neonatal complications. To outline this proinflammatory status, an innovative approach is represented by the measurement of proinflammatory cytokines. Among these biomarkers, B-cell-activating factor (BAFF) and platelet-activating factor (PAF) play a key role in metabolic regulation, immune response to infections, tissue homeostasis, and "food-related inflammation." The aim of the present study is to investigate the blood expression of BAFF and PAF in a cohort of pregnant women affected by obesity and diabetes compared with a control group of healthy pregnant women. METHODS: A prospective longitudinal cohort study has been conducted on pregnant women referred to Fondazione Policlinico Universitario Gemelli IRCCS in Rome. For each pregnant woman, a capillary sample was collected with a swab in three different consecutive evaluations carried out in the three trimesters of pregnancy. RESULTS: A total of 77 pregnant women have been enrolled. No significant differences in BAFF and PAF levels were longitudinally observed between groups. Focusing on the exposed group, in the third trimester of pregnancy, both PAF and BAFF levels were lower than the basal time. Among the selected group of patients who developed Gestational Diabetes, only PAF values were longitudinally lower when compared to other groups. The multivariate analysis showed that BAFF levels were positively correlated with thyroid-stimulating hormone levels. No macrosomia, no shoulder dystocia, no major perineal lacerations at birth, and no intrauterine growth restriction were observed in the whole population. CONCLUSIONS: This study supports the involvement of metabolic and proinflammatory biomarkers in the mechanisms related to pregnancy complications. Improving a good metabolic environment for obese and diabetic pregnant women could break the vicious cycle connecting inflammation, oxidative stress, and metabolic disorders.
Assuntos
Diabetes Gestacional , Obesidade Materna , Feminino , Humanos , Gravidez , Biomarcadores , Inflamação , Estudos Longitudinais , Obesidade/complicações , Fator de Ativação de Plaquetas , Estudos ProspectivosRESUMO
Increased B cell activating factor (BAFF) expression in patients with neuromyelitis optica spectrum disorder (NMOSD) is associated with B cell overstimulation, but the underlying mechanism remains unclear. This study aimed to reveal the emerging mechanisms that regulate BAFF expression in the inflammatory process of NMOSD. The results showed that the expression of miR-30b-5p was significantly decreased in NMOSD CD14+ monocytes compared with the normal control. Furthermore, we confirmed that metastasis-associated lung adenocarcinoma transcription 1 (MALAT1) is an upstream target of miR-30b-5p, and it could act as a ceRNA and absorb miR-30b-5p with reduced expression of miR-30b-5p. The low expression of miR-30b-5p could not bind to BAFF messenger RNA (mRNA), which resulted in the overexpression of both BAFF mRNA and protein expression. Overexpression of BAFF could bind to the corresponding receptors on B cells, which may initiate activation and proliferation of B cells and increase their production of autoantibodies. Therefore, these findings interpreted that excessive MALAT1 expression in NMOSD mononuclear macrophages led to increased BAFF expression by targeting miR-30b-5p, which caused B cell autoimmune reaction and autoantibodies production, aggravated the disease progression of NMOSD.
RESUMO
Breakdown of tolerance and abnormal activation in B cells is an important mechanism in the pathogenesis of Graves' disease (GD) and high levels of thyroid hormones (THs) can drive the progression of GD. However, the interactions between THs and abnormal activation of B cells in the context of GD are not well understood. The aim of this study was to investigate B cell-activating factor (BAFF) mediating the cross talk between THs and B cells and the possible underlying mechanisms. A high-level triiodothyronine (T3) mouse model was used to verify T3-mediated induction of overexpression of BAFF and B cell abnormal differentiation. The possible promotion of BAFF overexpression in the mice spleen macrophages during polarization to M1 by T3 was also studied. We showed that high levels of T3 can induce BAFF overexpression and lead to abnormal differentiation of B cells in the mice. While the overexpression of BAFF was observed across many tissue types in the mice, high levels of T3 could induce M1 macrophages polarization by IFN (interferon-gamma)-γ in the spleen of the mice, which in turn generated BAFF overexpression. Our findings provide a novel insight into the interactions between the endocrine and immune systems, as well as provide insight into the role of TH in the pathogenesis of GD.
Assuntos
Doença de Graves , Tri-Iodotironina , Animais , Camundongos , Tri-Iodotironina/metabolismo , Doença de Graves/metabolismo , Fator Ativador de Células B/metabolismo , Interleucina-4/metabolismo , Linfócitos B/metabolismo , Diferenciação CelularRESUMO
B-cell activating factor (BAFF) is a crucial cytokine for differentiation and survival of B-cells and correlates to disease activity in some auto-immune diseases. To evaluate BAFF as a biomarker for disease activity in chronic inflammatory demyelinating polyneuropathy (CIDP), serum BAFF levels were measured at varying disease stages: patients starting treatment, patients starting treatment withdrawal, patients in remission and healthy controls. Serum BAFF levels were elevated in patients compared to healthy controls, but did not differ between patients starting treatment and patients in remission. Serum BAFF levels did not change with or predict treatment response or relapse. Serum BAFF is not a responsive biomarker reflecting disease activity in CIDP.