Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies

Background. Tumor necrosis factor-alpha (TNF-α) is an important proinflammatory cytokine which plays an important role in the immunopathogenesis of Behcet’s disease (BD). B cell activating factor (BAFF) and its homolog A proliferation inducing ligand (APRIL) are members of the tumor necrosis factor family. BAFF binds to 3 receptors, B cell activating factor receptor (BAFF-R), transmembrane activator and calcium modulator ligand interactor (TACI), and B cell maturation antigen (BCMA) that are expressed by B cells.Objective. Estimation of the serum levels of TNF-α, APRIL, BAFF, and BCMA in patients with BD in an effort to evaluate their degree of involvement in the pathogenesis and development of BD.Patients and Methods. This study included 30 male patients fulfilling the international study group criteria for the diagnosis of BD. Twenty age-matched healthy male volunteers served as control. Serum samples were used for quantification of TNF-α, APRIL, BCMA, BAFF, and hsCRP using ELISA techniques.Results. The mean serum levels of TNF-α, APRIL, BCMA, and BAFF were more elevated in cases than in controls in a statistically significant manner(P<0.001). Positive correlation was observed between hs-CRP and BDCAF (Behcet’s disease current activity forum) index (r0.68,P<0.001). None of the TNF family members tested was affected by a positive pathergy test.Conclusions. Patients have significantly higher levels of TNF family members’ (TNF-α, BAFF, APRIL, and BCMA) compared to controls which might contribute to the pathogenesis of BD.

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Serum levels of galectin-3 in idiopathic inflammatory myopathies: a potential biomarker of disease activity

Rheumatology ◽

10.1093/rheumatology/keaa305 ◽

2020 ◽

Vol 60 (1) ◽

pp. 322-332

Author(s):

Eri Watanabe ◽

Kazunori Kato ◽

Takahisa Gono ◽

Emiko Chiba ◽

Chihiro Terai ◽

...

Keyword(s):

Disease Activity ◽

Interstitial Pneumonia ◽

Activity Index ◽

Biological Activities ◽

Inflammatory Cells ◽

Serum Levels ◽

Idiopathic Inflammatory Myopathies ◽

Inflammatory Myopathies ◽

Potential Biomarker ◽

Galectin 3

Abstract Objectives Galectin-3 is involved in various biological activities, including immune activations and fibrosis. Idiopathic inflammatory myopathies (IIMs) are autoimmune diseases of unknown aetiology, often complicated by interstitial lung disease (ILD). The aim of this study was to evaluate the expression of galectin-3 in sera and tissues of patients with IIM and assess the associations of galectin-3 with patient characteristics and disease activity. Results Serum galectin-3 levels were significantly higher in IIM patients than in healthy controls. The serum galectin-3 levels positively correlated with serum levels of inflammatory markers and proinflammatory cytokines/chemokines and the Myositis Intention-to-Treat Activity Index. Stratification analysis revealed that patients with IIM-associated ILD (IIM-ILD) had significantly higher levels of serum galectin-3 than those without IIM-ILD. In addition, patients with acute/subacute interstitial pneumonia had significantly higher levels of serum galectin-3 than those with chronic interstitial pneumonia. Furthermore, serum galectin-3 levels in IIM-ILD patients correlated with the radiological assessments of parenchymal lung involvement and treatment response. Immunohistochemical analysis revealed that galectin-3 was expressed in inflammatory cells of myositis and dermatitis sections, whereas in ILD sections, galectin-3 was expressed in interstitial fibrosis and inflammatory cells. Conclusion Galectin-3 may be involved in the pathogenesis of inflammatory and fibrotic conditions in IIM and can serve as a potential biomarker of disease activity, especially in patients with IIM-ILD.

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Serum BAFF (B-Cell Activating Factor of the TNF Family) Compared with Immunoglobulin Heavy-Chain Mutation Status, ZAP-70 and CD38 as a Predictor of Time to First Treatment in Early B-Cell Chronic Lymphocytic Leukemia.

Blood ◽

10.1182/blood.v110.11.3093.3093 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3093-3093

Author(s):

Stefano Molica ◽

Gaetano Vitelli ◽

Giovanna Cutrona ◽

Giovanna Digiesi ◽

Rosanna Mirabelli ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Heavy Chain ◽

Immunoglobulin Heavy Chain ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

B Cell Activating Factor ◽

Mutational Status ◽

Time To First Treatment ◽

Cell Chronic Lymphocytic Leukemia

Abstract We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia [CLL] (i.e, mutational status of the immunoglobulin heavy chain variable region [IgVH], ZAP-70- and CD38-expression) and serum levels of BAFF (B-cell activating factor of the TNF family) by evaluating the impact of these variables on the time to first treatment [TFT] in a series of 69 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA (R & D Systems, USA) we found that higher levels of BAFF characterized more frequently patients with Rai stage 0 (P=0.008) and mutated IgVH (P=0.03). In contrast, peripheral blood lymphocytosis (P=0.06), serum β2-m (P=0.159), LDH (P=0.333) and percentage of ZAP-70-positive (P=0.242) or CD38-positive B-CLL cells (P=0.142) did not reflect circulating levels of BAFF. The relationship among various bio-pathological parameters, analyzed by the multiple correspondence analysis (MCA), showed two different clinico-biological profiles. The first, characterized by higher BAFF serum levels (i.e., > 336 ng/mL), presence of mutation in the IgVH, low percentage of CD38-positive B-CLL cells (< 30%) and low LDH was associated with a stable pattern of disease generally not requiring therapy. The second, defined by lower BAFF levels, absence of mutation in the IgVH, high percentage of CD38- positive B-CLL cells and high LDH was associated with a more progressive pattern of disease and a shorter TFT. After a median follow-up time of 35 months (range, 2–120 months) 26 (37.6%) out of 69 patients experienced a need for chemotherapy. Kaplan-Meier estimates of patientsTFT, plotted after searching the best cut-off for BAFF (i.e., 336 ng/mL), demonstrated that low BAFF concentration was associated with a shorter TFT (median TFT 36 months) while median was not reached by patients with BAFF levels higher than 336 ng/mL (P<0.0001). Along with lower serum levels of BAFF (Hazard Ratio [HR], 0.19; P<0.0001), the univariate Cox proportional hazard model identified absence of mutation in IgVH (HR, 0.17; P<0.0001), CD38-positivity (HR, 3.32; P=0.01) and lower platelet count (HR, 0.19; P=0.03) as predictor of shorter TFT. Finally, in multivariate analysis only mutational status of IgVH (HR, 0.25; P=0.007) and serum concentration of BAFF (HR, 034; P=0.04) affected significantly TFT. Our results indicate that in early B-cell CLL clinico-biological profile including among other parameters BAFF may provide a useful insight into the complex interrelationship of prognostic variables and semplify their interpretation. The possible presence of BAFF isoform in B-CLL could peraphs account for the unexpected correlation between low soluble BAFF levels and poor clinical outcome in patients with early disease.

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AB0476 Serum Levels of Proliferation-Inducing Ligand, B-Cell Activating Factor, Antinuclear Autoantibodies and Markers of Inflammation in Patients with Primary Sjögren's Syndrome Compared To Patients with Sicca Symptoms without Diagnosis of pSS and with Healthy Subjects

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-eular.3309 ◽

2016 ◽

Vol 75 (Suppl 2) ◽

pp. 1069.1-1069

Author(s):

M. Maslinska ◽

E. Kontny

Keyword(s):

B Cell ◽

Healthy Subjects ◽

Serum Levels ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Markers Of Inflammation ◽

B Cell Activating Factor ◽

Antinuclear Autoantibodies ◽

Sicca Symptoms

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Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: Relationship with clinical findings

Vojnosanitetski pregled ◽

10.2298/vsp161115068m ◽

2019 ◽

Vol 76 (1) ◽

pp. 42-49

Author(s):

Radovan Mijanovic ◽

Sladjana Andrejevic ◽

Vladimir Jurisic ◽

Branka Bonaci-Nikolic

Keyword(s):

Autoimmune Diseases ◽

B Cell ◽

Common Variable Immunodeficiency ◽

Healthy Subjects ◽

Serum Levels ◽

Pulmonary Diseases ◽

Recurrent Infections ◽

B Cell Activating Factor ◽

Chronic Pulmonary Diseases ◽

Common Variable

Background/Aim. Common variable immunodeficiency (CVID) is an immunologically and clinically heterogeneous disorder. Disturbed cytokine production is implicated in dysfunctional immune response. The aim of this study was to investigated B-cell activating factor (BAFF) and interleukin (IL)- 10 levels in CVID patients. Methods. The study included 28 CVID patients diagnosed and followed during a 20-year period (mean follow-up 14.5 years). Control groups consisted of 4 patients with X-linked agammaglobulinemia (XLA) and 21 healthy subjects. According to clinical characteristics, the CVID patients were divided into four groups which partly overlap: chronic pulmonary diseases (n = 21), splenomegaly (n = 13), autoimmune diseases (n = 9) and patients with recurrent infections despite regular intravenous immunoglobulin (IVIg) substitution (n = 4). The serum levels of BAFF and IL-10 were measured by commercial ELISA. Results. The BAFF levels were found to be higher in all CVID patients compared to the healthy controls (p < 0.01). The most significant differences were observed in the patients with pulmonary diseases and splenomegaly (p < 0.0001). Also, concentrations of IL-10 were higher in all CVID patients in comparison with the XLA patients (p < 0.05) and healthy subjects (p < 0.01). A statistically significant positive correlation (r = 0.86; p < 0.01) was found between the levels of BAFF and IL-10 in the CVID patients with autoimmune diseases. We demonstrated that the CVID patients with chronic pulmonary diseases had higher levels of IL-10, while the CVID patients with recurrent infections had higher BAFF concentrations in comparison to the patients without these features (p < 0.05). Conclusion. In spite of the limited number of patients, this is the first report from Serbia, examining the serum levels of BAFF and IL-10 in the CVID patients. Our study showed significantly increased concentrations of serum BAFF and IL-10 in the patients with CVID compared to the healthy subjects. Further studies are needed to confirm our findings that the BAFF levels are more pronounced in patients with recurrent infections while IL-10 levels are higher in patients with chronic pulmonary diseases.

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Serum BAFF (B-CELL Activating Factor Of The TNF Family) predicts time to First Treatment in Early B-CELL Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood.v112.11.4158.4158 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4158-4158

Author(s):

Stefano Molica ◽

Gaetano Vitelli ◽

Giovanna Cutrona ◽

Giovanna Digiesi ◽

Rosanna Mirabelli ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Serum Concentration ◽

B Cell ◽

Serum Levels ◽

Lymphocytic Leukemia ◽

B Cell Activating Factor ◽

Mutational Status ◽

Time To First Treatment ◽

The Impact ◽

Cell Chronic Lymphocytic Leukemia

Abstract We analyzed the correlation between well-established biological parameters of prognostic relevance in B-cell chronic lymphocytic leukemia [CLL] (i.e, mutational status of the immunoglobulin heavy chain variable region [IgVH], ZAP-70− and CD38− expression) and serum levels of BAFF (B-cell activating factor of the TNF family) by evaluating the impact of these variables on the time to first treatment [TFT] in a series of 125 previously untreated Binet stage A B-cell CLL patients. By using a commercial ELISA (R & D Systems, USA) we found that higher levels of BAFF characterized more frequently females (P=0.01), patients with Rai stage 0 (P=0.03), mutated IgVH disease (P=0.008) and low ZAP-70 expression (P=0.04). In contrast, age (P=0.35), peripheral blood lymphocytosis (PBL)(P=0.09), hemoglobin (Hb) level (P=0.64), platelet (PLT) count (P=0.12), serum β2-m (P=0.49), LDH (P=0.85) and percentage of CD38-positive B-CLL cells (P=0.63) did not reflect circulating levels of BAFF. We used an optimal cut-point search to determine how to best split soluble BAFF data. Maximally selected log-rank statistics plots identified a BAFF serum concentration of 311 ng/mL as the best cut-off (P<0.0001). Accordingly, patients who had BAFF levels higher than 311 ng/mL experienced a longer TFT (median 108 months) in comparison to patients whose BAFF levels were lower than 311 ng/mL (median 30 months; P<0.0001). Along with serum concentration of BAFF, the univariate Cox proportional hazard model identified Rai substage I–II (P=0.003), lower PLT count (P=0.04), higher PBL count (P=0.01), increased LDH (P=0.01), ZAP-70 expression > 20% (P=0.02) and absence of mutation of IgVH (P<0.0001) as predictor of shorter TFT. In multivariate analysis only soluble BAFF (Hazard ratio [HR], 6.13; CI 95%, 2.31–16.25) and mutational status of IgVH, (HR= 2.99; CI 95% 1.33–6.76, P=0.008) maintained their discriminating power. The effects of BAFF on TFT were masked by mutational status of IgVH in patients with unmutated IgVH. However, serum levels of BAFF and mutational status of IgVH had a joint effect on TFT in patients with mutated IgVH which translates into a segregation of patients with mutated IgVH in two groups with different TFT according to BAFF levels (HR= 8.9; P<0.0001). Our results indicate that in early B-cell CLL biological profile including among other parameters soluble BAFF may provide a useful insight into the complex interrelationship of prognostic variables. Furthermore, BAFF along with mutational status of IgVH can be adequately used to predict clinical behaviour of patients with low biological risk.

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