scholarly journals Association of Platelet Binding to Lymphocytes with B Cell Abnormalities and Clinical Manifestations in Systemic Lupus Erythematosus

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Carlos Zamora ◽  
Elide Toniolo ◽  
Cesar Diaz-Torné ◽  
Elisabet Cantó ◽  
Berta Magallares ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
B Lymphocytes ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Cell Function ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Renal Manifestation ◽  
Promising Therapeutic Approach

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach.

scholarly journals Artemisinin derivative SM934, influences the activation, proliferation, differentiation and antibody-secreting capacity of β-cells in systemic lupus erythematosus mice via inhibition of TLR7/9 signaling pathway

2021 ◽  
Vol 18 (7) ◽  
pp. 1391-1396
Author(s):  
Yajuan Li ◽  
Lixin Zhao ◽  
Xuehui Yang ◽  
Jing Chen ◽  
Wenjing Xu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Artemisinin Derivative ◽  
Systemic Lupus ◽  
Dose Dependent

Purpose: To study the influence of artemisinin derivative, SM934 on activation, proliferation, differentiation and antibody-secreting capacity of B cells of systemic lupus erythematosus (SLE) mice, and the underlying mechanism. Methods: Female MRL/lpr mice (n = 60) were randomly assigned to four groups of 15 mice each: SLE, 2.5 mg/kg SM934; 5 mg/kg SM934, and 10 mg/kg SM934 groups. Serum levels of interleukins 6, 10, 17 and 21 (IL-6, IL-17, IL-10 and IL-21) were determined. The secretions of immunoglobulins G and M (IgG and IgM) by B cells were determined. The population of B lymphocyte subtypes was determined flow cytometrically. The expressions of Blimp-1 and Bcl-6, Toll-like receptors 7 and 9 (TLR7 and TLR9) mRNAs were determined. Results: SLE-induced upregulation of serum IL-10, IL-6, IL-17 and IL-21 was significantly and dosedependently reduced following a 2-month treatment with SM934 (p < 0.01). Treatment with SM934 significantly and dose-dependently accentuated B cell germinal center B cell populations, but significantly and dose-dependently decreased the populations of plasma and activated B cells (p < 0.01). The splenic levels of IgG and IgM were decreased in a dose-dependent fashion after 8 weeks of treatment (p < 0.01). Artemisinin derivative SM934 decreased the expression of Blimp-1, and upregulated the expression of Bcl-6, both in a dose-dependent manner (p < 0.01). Moreover, SM934 decreased the mRNA expressions of TLR7 and TLR9 in a dose-based manner (p < 0.01). Conclusion: Artemisinin derivative SM934 mitigates LSE syndromes by suppressing the TLR-induced B-cell stimulation and plasma cell generation

Next stop in the treatment of refractory systemic lupus erythematosus: B-cell targeted combined therapy

Lupus ◽  
2020 ◽  
Vol 30 (1) ◽  
pp. 134-140
Author(s):  
Margarida Matos Bela ◽  
Gerard Espinosa ◽  
Ricard Cervera
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Randomized Clinical Trials ◽  
Wide Spectrum ◽  
Combined Therapy ◽  
Clinical Manifestations ◽  
Drug Regimen ◽  
Systemic Lupus

Background: Systemic lupus erythematosus (SLE) is an autoimmune condition with a wide spectrum of clinical manifestations encompassing most organs and systems. Its treatment approach includes different immunomodulatory treatments, of which B-cell targeted therapies are part of. Rituximab (an anti-CD20 antibody) had encouraging results in observational studies but failed when tested in clinical trials. It is theorized that this could have been partially due to BAFF upregulation, leading to rituximab failure. Therefore, targeting BAFF with belimumab after rituximab therapy, may have a synergic effect in SLE. Objective: We review the available observational data regarding sequential rituximab/belimumab therapy in SLE patients. Results: Twenty-four patients from 6 studies were included. The results suggest a benefit with this combined therapy, with reduction of the mean SLEDAI. However, there was significant drug regimen and patient selection heterogeneity. Conclusion: Further randomized clinical trials are needed to examine this drug sequencing protocol in SLE patients.

Hormonal regulation of B-cell function and systemic lupus erythematosus

Lupus ◽  
2008 ◽  
Vol 17 (6) ◽  
pp. 528-532 ◽  
Author(s):  
JFG Cohen-Solal ◽  
V Jeganathan ◽  
L Hill ◽  
D Kawabata ◽  
D Pinto-Rodriguez ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Hormonal Regulation ◽  
Cell Function ◽  
Systemic Lupus ◽  
B Cell Function

scholarly journals AB0009 ASSOCIATION BETWEEN POLYMORPHISMS OF BANK1 AND MANIFESTATIONS OF SLE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1308.1-1308
Author(s):  
D. D. González-Castillo ◽  
R. E. Barbosa-Cobos ◽  
G. E. Lugo Zamudio ◽  
M. A. Saavedra ◽  
R. E. Sánchez-Briones ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Association Study ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Mexican Population ◽  
Physical Interaction ◽  
Systemic Lupus ◽  
Weinberg Equilibrium ◽  
Hardy Weinberg Equilibrium

Background:BANK1encodes an adapter/scaffold protein primarily expressed in B cells, which is involved in cell signaling and activation. Genome-wide association studies (GWAS) have identified differentBANK1single nucleotide variants (SNVs) associated with SLE primarily in European or Asian-derived populations. Interestingly, we recently have documented an association between this gene and susceptibility to systemic lupus erythematosus (SLE) in Mexican population.Objectives:To determine whether theBANK1R61H (rs10516487G/A) and A383T (rs3733197G/A) SNVs are associated with clinical and immunological manifestations in SLE.Methods:Our study included 123 Mexican women with SLE (SLICC 2012 criteria). Genotyping of the twoBANK1SNVs were obtained by TaqMan probes and real-time PCR. An association study was performed between the alleles and genotypes ofBANK1R61H and A383T with the clinical and immunological manifestations included in the SLE SLICC classification criteria. Hardy-Weinberg equilibrium and an association study was performed using Finetti, apvalue ≤ 0.05 indicated association.Results:We identify an average age of 38.5±12. Cases and controls remained in Hardy-Weinberg equilibrium. An association with susceptibility to SLE was found between genotypes of the twoBANK1SNVs and joint manifestations (rs1051487G/A; AA + GA vs GG, OR 4.45,p=0.004, rs3733197G/A; AA + GA vs GG, OR 2.66,p=0.032, respectively), as well as with protection for neurological and renal involvement (rs1051487G/A, OR 0.16,p=0.02, rs3733197G/A; OR 0.40,p=0.02, respectively) (Table 1a and b). No association was found with other clinical manifestations.Conclusion:Our data in the Mexican population show that bothBANK1R61H and A383T SNVs are risk factors for synovitis. On the other hand, theseBANK1R61H and A383T variants are protective factors for neurological and renal damage, respectively.References:[1]Ramírez-Bello J, Jiménez-Morales S, Montufar-Robles I, et al. BLK and BANK1 polymorphisms and interactions are associated in Mexican patients with systemic lupus erythematosus. Inflamm Res. 2019;68:705-13[2]J. De Azevêdo Silva, C. Addobbati, P. Sandrin-Garcia and S. Crovella. Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations. Current Genomics. 2014;15:52-65[3]Sánchez E, Rasmussen A, Riba L, Acevedo E, Kelly J, Langefeld CD, et al. Impact of Genetic Ancestry and Socio-Demographic Status on the Clinical Expression of Systemic Lupus Erythematosus in Amerindian-European Populations. Arthritis Rheum. 2012; 64(11):3687–3694[4]Castillejo-López C, Delgado-Vega AM, Wojcik J, et al. Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK. Ann Rheum Dis. 2012;71:136–42[5]Kozyrev SV, Abelson AK, Wojcik J, et al. Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:211-6Disclosure of Interests:None declared

scholarly journals B lymphocyte stimulator modulates number and function of endothelial progenitor cells in systemic lupus erythematosus

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Francesca Romana Spinelli ◽  
Cristiana Barbati ◽  
Fulvia Cecarelli ◽  
Francesca Morello ◽  
Tania Colasanti ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Endothelial Cells ◽  
B Cell ◽  
Progenitor Cells ◽  
Lupus Erythematosus ◽  
B Lymphocyte ◽  
Ex Vivo ◽  
Systemic Lupus ◽  
B Lymphocyte Stimulator

Abstract Background Circulating endothelial progenitor cells (EPCs) are biologic markers of endothelial function. In patients with systemic lupus erythematosus (SLE), the numerical reduction and functional impairment of EPCs contribute to the endothelial dysfunction. Through ex vivo and in vitro studies, we aimed at evaluating the effects of B lymphocyte stimulator (BLyS) on EPC colonies and endothelial cells and also investigating BLyS receptor expression on these cells. Methods EPCs were isolated from peripheral blood mononuclear cells (PBMC). In order to evaluate their ability to form colonies, EPCs were cultured on fibronectin-coated dishes and incubated with BlyS alone or BlyS and belimumab. Apoptosis of EPCs and endothelial cell line EA.hy926 was evaluated after 6, 12, and 24 h of incubation with BLyS and after 6 h with BLyS and belimumab. The expression of B cell activating factor-receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI) on EPCs and EA.hy926 was analyzed by cytofluorimetry. Results The number of EPC colonies was lower in patients than in controls. Moreover, the colonies from SLE patients were poorly organized compared to controls; the addition of belimumab restored the colony structure. Incubation with BLyS induced apoptosis of EPCs and EA.hy926 that was inhibited by the co-incubation with belimumab. BAFF-R and BCMA were expressed on both EPCs and EA.hy926, while TACI was expressed only on EPCs. Conclusions EPCs and endothelial cells preferentially express BAFF-R which could be involved in the pro-apoptotic effect of BlyS. Belimumab administration seems to restore the quantitative and qualitative changes of EPC colonies both ex vivo and in vitro.

scholarly journals Clinical Efficacy of Belimumab in Patients with Systemic Lupus Erythematosus and Headache. A Report of Two Cases

2021 ◽  
Author(s):  
Takao Kodera ◽  
Tomomi Tsutsumi ◽  
Yumiko Oka ◽  
Tomoki Takeda ◽  
Yuko Shirota ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
B Lymphocytes ◽  
Lupus Erythematosus ◽  
Conventional Therapy ◽  
B Lymphocyte ◽  
Systemic Lupus ◽  
Potential Benefits ◽  
B Lymphocyte Stimulator ◽  
Early Effects

Abstract Intractable headache, one of the manifestations of neuropsychiatric systemic lupus erythematosus, is difficult to diagnose and determine an effective treatment. In addition to conventional therapy according to the type of headache, the treatment should be conducted considering the disease activity of systemic lupus erythematosus rather than the headache. We report two patients with intractable headache who were successfully treated using belimumab therapy. The headaches in both patients were relieved after 2 weeks of belimumab administration. The neutralization of B lymphocyte stimulator and reduced production of cytokines from B lymphocytes might contribute to the early effects. The potential benefits of using belimumab as an additional immunosuppressant for treating intractable headache complicated with systemic lupus erythematosus have been discussed.

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