Preferential increase of B-cell activating factor in the cerebrospinal fluid of neuromyelitis optica in a white population

2010 ◽  
Vol 16 (12) ◽  
pp. 1453-1457 ◽  
Author(s):  
Adi Vaknin-Dembinsky ◽  
Livnat Brill ◽  
Naama Orpaz ◽  
Oded Abramsky ◽  
Dimitrios Karussis
Keyword(s):  
Cerebrospinal Fluid ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Cell Activation ◽  
B Cell Activation ◽  
White Population ◽  
B Cell Activating Factor ◽  
Healthy Donors ◽  
Elisa Technique ◽  
Csf Levels

Background: Anti-aquaporin-4 antibodies are believed to have a central pathogenetic role in neuromyelitis optica (NMO). B-cell activating factor (BAFF) is one of the crucial factors that determines the fate and survival of B cells and may play a role in induction of antibody-mediated autoimmunity. Objectives: To evaluate the blood and cerebrospinal fluid (CSF) levels of BAFF in NMO and multiple sclerosis (MS) patients. Methods: Peripheral blood samples were collected from 21 definite NMO patients, 22 healthy controls and 45 MS patients and CSF from 8 NMO and 11 MS patients. BAFF levels were measured using an ELISA technique. Results: We found significantly higher levels of BAFF in the CSF of NMO patients compared with that in MS (215.6 ± 41 pg/ml in NMO and 77.4 ± 11 pg/ml in MS, p < 0.001). There were no differences in serum BAFF levels between NMO, MS and healthy donors. MS patients treated with interferon-beta (IFNβ) or glatiramer acetate (GA) had significantly higher serum BAFF levels, as compared with untreated patients (1227 ± 203 pg/ml in untreated MS, 2253 ± 83.4 pg/ml in GA-treated, p < 0.01, and 2106 ± 277.9 pg/ml in interferon-treated, p < 0.05) Conclusion: The presence of increased BAFF, a soluble factor associated with B-cell activation in the proximity of the disease target organ (CSF) in NMO, and its increase in association with immunomodulating treatments, may help our understanding of the immunopathogenetic mechanisms involved in this disease and contribute to more successful and targeted therapeutic intervention.

Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study

2016 ◽  
Vol 22 (9) ◽  
pp. 1192-1201 ◽  
Author(s):  
Katalin T Kovacs ◽  
Sudhakar Reddy Kalluri ◽  
Antonio Boza-Serrano ◽  
Tomas Deierborg ◽  
Tunde Csepany ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Neuromyelitis Optica ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Rare Condition ◽  
B Cell Activation ◽  
Systemic Lupus ◽  
Cytokines And Chemokines ◽  
Ifn Γ

Background: Neuromyelitis optica (NMO)–systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. Objective: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. Methods: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. Results: AQP4-IgG1 was present 1–2–5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC ( p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA ( p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE ( p<0.05). Conclusions: AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.

scholarly journals Frequency and syndrome specificity of antibodies to aquaporin-4 in neurological patients with rheumatic disorders

2011 ◽  
Vol 17 (9) ◽  
pp. 1067-1073 ◽  
Author(s):  
Sven Jarius ◽  
Christian Jacobi ◽  
Jerome de Seze ◽  
Helene Zephir ◽  
Friedemann Paul ◽  
...  
Keyword(s):  
B Cell ◽  
Rheumatic Diseases ◽  
Neuromyelitis Optica ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Transverse Myelitis ◽  
B Cell Activation ◽  
Serum Samples ◽  
Neurological Patients ◽  
Spectrum Disorders

Background: A new autoantibody (termed NMO-IgG, or AQP4-Ab) has recently been described in patients with neuromyelitis optica (NMO) and its formes frustes, longitudinally extensive transverse myelitis (LETM) and recurrent optic neuritis (rON). However, AQP4-Ab has been found also in patients with co-existing rheumatic diseases such as systemic lupus erythematosus (SLE) or Sjögren’s syndrome (SS), conditions which are characterized by broad, polyspecific B cell activation. Objectives: In this study, we aimed at evaluating the syndrome specificity and frequency of AQP4-Ab in patients with rheumatic diseases and neurological symptoms. Methods: For this purpose, serum samples from 109 neurological patients with established connective tissue disorders (CTD) ( n = 54), possible CTD ( n = 42), or vasculitis ( n = 13) were analysed for the presence of AQP4-Ab by a cell-based assay employing recombinant human AQP4. Results: AQP4-Ab was detectable in 31/40 (78%) patients with CTD and NMO spectrum disorders (median titre, 1:1000) but in none of the samples obtained from patients with CTD or vasculitis and neurological disorders other than NMO, LETM, or rON ( n = 69). Conclusion: The high syndrome specificity of the antibody for neuromyelitis optica spectrum disorders (NMOSDs) in patients with CTD supports the concept of AQP4-Ab being involved in the pathogenesis of these neurological conditions, and argues against AQP4-Ab simply being part of the polyclonal B cell activation generally associated with rheumatic diseases. Moreover, the finding that AQP4-Ab is present in patients with CTD and co-existing NMOSD with approximately the same frequency as in patients without CTD strengthens the case of CTD and AQP4-Ab positive NMOSD representing two co-existing yet distinct entities in the majority of patients.

B-cell activating factor (BAFF) promotes CpG ODN-induced B cell activation and proliferation

2011 ◽  
Vol 271 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Rachelle M. Buchanan ◽  
Yurij Popowych ◽  
Natasha Arsic ◽  
Hugh G.G. Townsend ◽  
George K. Mutwiri ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
Cpg Odn ◽  
B Cell Activation ◽  
B Cell Activating Factor

Interferon-gamma and B-cell Activating Factor (BAFF) promote bovine B cell activation independent of TLR9 and T-cell signaling

2012 ◽  
Vol 145 (1-2) ◽  
pp. 453-463 ◽  
Author(s):  
Rachelle Buchanan ◽  
Yurij Popowych ◽  
Crystal Dagenais ◽  
Natasa Arsic ◽  
George K. Mutwiri ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Signaling ◽  
B Cell ◽  
Interferon Gamma ◽  
Cell Activation ◽  
B Cell Activation ◽  
T Cell Signaling ◽  
B Cell Activating Factor

scholarly journals Longitudinally persistent cerebrospinal fluid B-cells resist treatment in multiple sclerosis

2018 ◽  
Author(s):  
Ariele L. Greenfield ◽  
Ravi Dandekar ◽  
Akshaya Ramesh ◽  
Erica L. Eggers ◽  
Hao Wu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Variable Region ◽  
B Cell Activation ◽  
Cell Dynamics ◽  
Autoimmune Pathology ◽  
B Cell Subsets

AbstractB-cells are key contributors to chronic autoimmune pathology in multiple sclerosis (MS). Clonally related B-cells exist in the cerebrospinal fluid (CSF), meninges, and central nervous system (CNS) parenchyma of MS patients. Longitudinally stable CSF oligoclonal band (OCB) antibody patterns suggest some local CNS B-cell persistence; however, the longitudinal B-cell dynamics within and between the CSF and blood remain unknown. We sought to address this by performing immunoglobulin heavy chain variable region repertoire sequencing on B-cells from longitudinally collected blood and CSF samples of MS patients (n=10). All patients were untreated at the time of the initial sampling; the majority (n=7) were treated with immune modulating therapies 1.2 (+/−0.3 SD) years later during the second sampling. We found clonal persistence of B-cells in the CSF of five patients; these B-cells were frequently immunoglobulin (Ig) class-switched and CD27+. We identified specific blood B-cell subsets that appear to provide input into CNS repertoires over time. We demonstrate complex patterns of clonal B-cell persistence in CSF and blood, even in patients on high-efficacy immune modulating therapy. Our findings support the concept that peripheral B-cell activation and CNS-compartmentalized immune mechanisms are in part therapy-resistant.

Analysis of B-cell activation of cerebrospinal fluid lymphocytes in multiple sclerosis

Neurology ◽  
1983 ◽  
Vol 33 (10) ◽  
pp. 1305-1305 ◽  
Author(s):  
A. I. Levinson ◽  
M. Sandberg-Wollheim ◽  
R. P. Lisak ◽  
B. Zweiman ◽  
K. Sjogren ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation

scholarly journals Anti-CD40 antibody KPL-404 inhibits T cell-mediated activation of B cells from healthy donors and autoimmune patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
John Marken ◽  
Sujatha Muralidharan ◽  
Natalia V. Giltiay
Keyword(s):  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cytokine Production ◽  
B Cell Activation ◽  
Cell Responses ◽  
Healthy Donors ◽  
B Cell Responses

Abstract Background CD40-CD40L is a key co-stimulatory pathway for B cell activation. As such, its blockade can inhibit pathogenic B cell responses in autoimmune diseases, such as Sjogren’s syndrome (SjS) and systemic lupus erythematosus (SLE). In this study, we examined the in vitro effects of KPL-404, a humanized anti-CD40 monoclonal antibody (Ab), on primary human B cells derived from either healthy donors (HD) or autoimmune patients and compared them to the effects of G28-5, a partially antagonistic anti-CD40 antibody. Methods PBMCs from HD or SjS and SLE patients were cultured in high-density cell cultures in the presence of IgG4 isotype control or anti-CD40 Abs KPL-404 or G28-5. Cells were stimulated with anti-CD3/CD28 cross-linking reagent ImmunoCult (IC) to induce CD40L-CD40-mediated B cell responses. B cell proliferation and activation, measured by dilution of proliferation tracker dye and the upregulation of CD69 and CD86, respectively, were assessed by flow cytometry. Anti-CD40 Ab cell-internalization was examined by imaging flow cytometry. Cytokine release in the PBMC cultures was quantified by bead-based multiplex assay. Results KPL-404 binds to CD40 expressed on different subsets of B cells without inducing cell depletion, or B cell proliferation and activation in in vitro culture. Under the same conditions, G28-5 promoted proliferation of and increased CD69 expression on otherwise unstimulated B cells. KPL-404 efficiently blocked the CD40L-CD40-mediated activation of B cells from HD at concentrations between 1 and 10 μg/ml. Treatment with KPL-404 alone did not promote cytokine production and blocked the production of IFNβ in healthy PBMC cultures. KPL-404 efficiently blocked CD40L-CD40-mediated activation of B cells from patients with SjS and SLE, without affecting their anti-IgM responses or affecting their cytokine production. Consistent with the differences of their effects on B cell responses, KPL-404 was not internalized by cells, whereas G28-5 showed partial internalization upon CD40 binding. Conclusions Anti-CD40 mAb KPL-404 showed purely antagonistic effects on B cells and total PBMCs. KPL-404 inhibited CD40L-CD40-mediated B cell activation in PBMC cultures from both healthy controls and autoimmune patients. These data support the therapeutic potential of CD40 targeting by KPL-404 Ab for inhibiting B cell responses in SjS and SLE.

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