scholarly journals New ELISA for B Cell–Activating Factor

2009 ◽  
Vol 55 (10) ◽  
pp. 1843-1851 ◽  
Author(s):  
Laëtitia Le Pottier ◽  
Boutahar Bendaoud ◽  
Yves Renaudineau ◽  
Pierre Youinou ◽  
Jacques-Olivier Pers ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Polyclonal Antibodies ◽  
Response To Therapy ◽  
Optimization Process ◽  
Serum Concentrations ◽  
B Cell Activating Factor ◽  
Capture Antibody

Abstract Background: The B cell–activating factor of the TNF family (BAFF) is upregulated in autoimmune diseases, but a number of conflicting results have cast doubts on the reliability of the ELISA protocols currently used for its quantification. This situation led us to develop a new ELISA for the measurement of BAFF. Methods: BAFF was purified for use alongside nonglycosylated recombinant BAFF. Two monoclonal antibodies (mAbs) and two polyclonal antibodies (pAbs) to BAFF were used. Results: The optimization process showed that the pAb format was preferable to the mAb format as capture antibody, because the pAbs recognized the glycosylated as well as the nonglycosylated forms of BAFF. The most efficient pair of Abs involved using the unconjugated form of a goat pAb to capture BAFF and the same biotinylated goat pAb to detect bound BAFF. This ELISA was not influenced by the presence of rheumatoid factor. Conclusions: This new ELISA helped provide insights into why serum concentrations of BAFF vary between studies for a given population of patients. It is a reliable tool for the management of the diseases in which BAFF is an indication of response to therapy.

B Cell-activating Factor and its Targeted Therapy in Autoimmune Diseases

2021 ◽  
Author(s):  
Yidan Zhang ◽  
Jie Tian ◽  
Fan Xiao ◽  
Leting Zheng ◽  
Xiaoxia Zhu ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Autoimmune Diseases ◽  
B Cell ◽  
B Cell Activating Factor

Characterization of Antibodies Direct against the Idiotypic VK3 Chain of HCV-Related Type-II Mixed Cryoglobulinemia and B-Cell Proliferations

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4988-4988
Author(s):  
Valli De Re ◽  
Maria Paola Simula ◽  
Alessandro Pavan ◽  
Dolores Marin ◽  
Laura Caggiari ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cells ◽  
Western Blot ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Light Chain ◽  
B Cell Lymphoma ◽  
Type Ii ◽  
Cell Proliferations

Abstract Autoimmune type-II cryoglobulinemia (MC) is sustained by clonal/oligoclonal B-cell populations such the disease may be considered an “indolent B-cell lymphoma (NHL) “ and may favor overt NHL development. HCV-antigen driven mechanism induces B-cell proliferations. Clonal B-cells demonstrate a restricted used of variable genes to construct the B-cell receptor (BCR) and a homology between BCR functional regions and autoimmune rheumatoid factor (RF) activity. We underline the BCR unique repertoire with frequent rheumatoid factor activity also in other autoimmune disorders associated to NHL development as Sjogren’s syndrome and rheumatoid arthritis. All together these BCRs are characterized by their high degree of idiotypic (Id) cross reactivity. Particularly the K chain V3-20/15 is frequently found in subject with positive HCV antibody. Id is a clonamarker expressedby B cells, thus is an ideal target for immunotherapy. The evidence of few Id presented in the NHL subgroup above reported constitute the rational for the development of antibodies and recombinant proteins that use shared Id among different NHL. Five monoclonal antibodies have been produced in our laboratory toward the VK3-20 region of a subject HCV+ with NHL. Epitopes recognized has been performed using epitope excision approach. A fine determination of the antibodies activities toward specific amino acids, possibly common to different individuals, are in progress. Monoclonal antibodies reactivity has been tested in vitro in ELISA, western blot and cytofluorimetry. Apoptosis and SyK/ERK phosphorylation pathways induced following BCR cross-linking of antiId murine IgG will be performed. All the antibodies were reactive in Elisa against the VK3-Ig light chain. Two of these antibodies showed a reactivity against the light chain of cryoprecipitated immunocomplexes from several patients in western blot, and by cytofluorimter they recognised two lymphoma B-cell lines.

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

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.

scholarly journals Two-site immunofluorometric assay of intact salmon calcitonin with improved sensitivity

1997 ◽  
Vol 43 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Haiqin Rong ◽  
Leonard J Deftos ◽  
Hong Ji ◽  
Elisabet Bucht
Keyword(s):  
Monoclonal Antibody ◽  
Detection Limit ◽  
Polyclonal Antibody ◽  
Salmon Calcitonin ◽  
Polyclonal Antibodies ◽  
Pharmacokinetic Studies ◽  
Human Calcitonin ◽  
Plasma Samples ◽  
Serum Concentrations ◽  
Capture Antibody

Abstract We recently developed a two-site immunofluorometric assay (IFMA) of salmon calcitonin (SCT) by DELFIA (dissociation enhancement lanthanide fluoroimmunoassay) technique using the same polyclonal antibodies both for “catching” the antigen and for signaling. In the present study we used a monoclonal antibody to SCT 1–11 as the capture antibody. This antibody was biotinylated before use in streptavidin-coated microtitration plates. The polyclonal antibody labeled with Eu chelate was used as a signaling marker. This combination of antibodies resulted in an assay that was three to four times more sensitive than the previous IFMA, with a detection limit of 0.3 pmol/L serum. Intact SCT 1–32 was detected by the assay (recoveries 94–96%), but not the fragments SCT 1–11 and SCT 10–32 or human calcitonin. Dilutions of plasma samples containing SCT were parallel to the calibration curve of SCT 1–32. Pharmacokinetic studies of SCT, 100 IU administered intramuscularly to 10 men, indicated peak serum concentrations of 32–128 pmol/L within 10–20 min with apparent half-life of 56 ± 18 min (mean ± SD). This new assay will allow study of the pharmacokinetics of new calcitonin preparations that do not require injection.

scholarly journals New biomarkers in SLE: from bench to bedside

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_5) ◽  
pp. v12-v18 ◽  
Author(s):  
Riccardo Capecchi ◽  
Ilaria Puxeddu ◽  
Federico Pratesi ◽  
Paola Migliorini
Keyword(s):  
B Cell ◽  
Response To Therapy ◽  
Disease Course ◽  
Pathogenetic Mechanism ◽  
Cell Compartment ◽  
Local Regulation ◽  
Complement Proteins ◽  
Urine Biomarkers ◽  
B Cell Activating Factor ◽  
New Biomarkers

Abstract Biomarkers may have a diagnostic or monitoring value, or may predict response to therapy or disease course. The aim of this review is to discuss new serum and urinary biomarkers recently proposed for the diagnosis and management of SLE patients. Novel sensitive and specific assays have been proposed to evaluate complement proteins, ‘old’ biomarkers that are still a cornerstone in the management of this disease. Chemokines and lectins have been evaluated as surrogate biomarkers of IFN signature. Other cytokines like the B cell activating factor (BAFF) family cytokines are directly related to perturbations of the B cell compartment as key pathogenetic mechanism of the disease. A large number of urine biomarkers have been proposed, either related to the migration and homing of leukocytes to the kidney or to the local regulation of inflammatory circuits and the survival of renal intrinsic cells. The combination of traditional disease-specific biomarkers and novel serum or urine biomarkers may represent the best choice to correctly classify, stage and treat patients with SLE.

scholarly journals Monitoring anti-B cell immunotherapies in autoimmune diseases: Go with the flow. A Position Paper of the Italian Society for Clinical Cell Analysis (ISCCA)

2019 ◽  
Vol 1 (2) ◽  
pp. 52-62
Author(s):  
Bruno Brando ◽  
Arianna Gatti ◽  
Alfredo Maria Lurati ◽  
Paola M.L. Faggioli
Keyword(s):  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cells ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Cell Activation ◽  
Biological Effects ◽  
Individual Response ◽  
Anti Cd20

During the past decades autoimmune diseases have been usually treated with immunosuppressive drugs mostly active on T-Cell mediated responses. Only in recent years, with our extended knowledge of the pathogenic mechanisms of autoreactive disorders and the tremendous development of new therapeutic monoclonal antibodies, anti-B-Cell therapies have emerged as a new option for treating autoimmune diseases. The rationale for this changeover from T-Cell to B-Cell targeted therapies resides in the recently accumulated evidence of the role of B-Cells in the pathogenesis of autoimmune diseases and in the generation of tissue damage. Targeting memory and effector BCells may then disrupt the production of pathogenic antibodies, counteract the role of B-Cells in sustaining antigen presentation to T-Cells and block the synthesis of B-Cell activation cytokines. The anti-CD20 monoclonal antibody Rituximab was first introduced more than 20 years ago for the treatment of CD20+ chronic B-lymphoproliferative disorders, and was then successfully experimented in the treatment of an ever-increasing spectrum of autoimmune diseases. Newer anti-CD20 monoclonal antibodies have been introduced more recently, which vary in their biological effects. The need for laboratory indicators that may help the rational usage and follow-up of anti-CD20 treatments has now emerged, due to the high variability of individual response, to the markedly different outcomes in the various diseases and to the controversial role of pathogenic autoantibodies as indicators of disease activity. Flow cytometric (FCM) analyses to identify and enumerate the B-cell functional subsets in the peripheral blood have been developed in recent years. They can be used to assess the degree and the persistence of memory B-Cell depletion, the quality and the timing of B-Cell reconstitution, along with the highly sensitive FCM counting technique needed for the detection of extremely low cell levels. The long-term aim of this innovative approach is to provide clinicians with a tool for a safer and more rational usage of anti-CD20 agents.

scholarly journals Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Agata N. Burska ◽  
Laura Hunt ◽  
Marjorie Boissinot ◽  
Rocky Strollo ◽  
Brent J. Ryan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Rheumatoid Factor ◽  
Posttranslational Modifications ◽  
B Cell Development ◽  
Long Time ◽  
Anticitrullinated Protein Antibodies ◽  
Human B Cell

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell developmentin vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential.

scholarly journals Role of B-Cell Activating Factor (BAFF) in Inflammatory Bowel Disease

Diagnostics ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 45
Author(s):  
Marko Kumric ◽  
Piero Marin Zivkovic ◽  
Tina Ticinovic Kurir ◽  
Josip Vrdoljak ◽  
Marino Vilovic ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Bowel Disease ◽  
Response To Therapy ◽  
Current Evidence ◽  
Therapeutic Implications ◽  
B Cell Activating Factor ◽  
Inflammatory Bowel

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

Genetic variation in recipient B-cell activating factor modulates phenotype of GVHD

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1140-1144 ◽  
Author(s):  
William B. Clark ◽  
Kristin D. Brown-Gentry ◽  
Dana C. Crawford ◽  
Kang-Hsien Fan ◽  
Jennifer Snavely ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
B Cell ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Odds Ratio ◽  
Chronic Gvhd ◽  
B Cell Activating Factor

Abstract B-cell activating factor (BAFF) single nucleotide polymorphisms (SNPs) are associated with autoimmune diseases. Because patients with classic and overlap chronic GVHD (cGVHD) have features of autoimmune diseases, we studied the association of recipient and/or donor BAFF SNPs with the phenotype of GVHD after allogeneic stem cell transplantation. Twenty tagSNPs of the BAFF gene were genotyped in 164 recipient/donor pairs. GVHD after day 100 occurred in 124 (76%) patients: acute GVHD (aGVHD) subtypes (n = 23), overlap GVHD (n = 29), and classic cGVHD (n = 72). In SNP analyses, 9 of the 20 tag SNPs were significant comparing classic/overlap cGVHD versus aGVHD subtypes/no GVHD. In multivariate analyses, 4 recipient BAFF SNPs (rs16972217 [odds ratio = 2.72, P = .004], rs7993590 [odds ratio = 2.35, P = .011], rs12428930 [odds ratio2.53, P = .008], and rs2893321 [odds ratio = 2.48, P = .009]) were independent predictors of GVHD subtypes, adjusted for conventional predictors of cGVHD. This study shows that genetic variation of BAFF modulates GVHD phenotype after allogeneic stem cell transplantation.

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