Construction and Function of Two Cys146-Mutants with High Activity, Derived from Recombinant Human Soluble B Lymphocyte Stimulator

2004 ◽  
Vol 136 (1) ◽  
pp. 73-79 ◽  
Author(s):  
G. Chen
Keyword(s):  
High Activity ◽  
B Lymphocyte ◽  
B Lymphocyte Stimulator ◽  
And Function

scholarly journals Decision Making for Treatment After ACL Injury From an Orthopaedic Surgeon and Patient Perspective: Results From the NACOX Study

2021 ◽  
Vol 9 (4) ◽  
pp. 232596712110050
Author(s):  
Hanna Tigerstrand Grevnerts ◽  
Sofi Sonesson ◽  
Håkan Gauffin ◽  
Clare L. Ardern ◽  
Anders Stålman ◽  
...  
Keyword(s):  
Decision Making ◽  
High Activity ◽  
Treatment Decision ◽  
Acl Injury ◽  
Treatment Decisions ◽  
Activity Level ◽  
Knee Instability ◽  
Acl Injuries ◽  
Patient Reported ◽  
And Function

Background: In the treatment of anterior cruciate ligament (ACL) injuries, there is little evidence of when and why a decision for ACL reconstruction (ACLR) or nonoperative treatment (non-ACLR) is made. Purpose: To (1) describe the key characteristics of ACL injury treatment decisions and (2) compare patient-reported knee instability, function, and preinjury activity level between patients with non-ACLR and ACLR treatment decisions. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 216 patients with acute ACL injury were evaluated during the first year after injury. The treatment decision was non-ACLR in 73 patients and ACLR in 143. Reasons guiding treatment decision were obtained from medical charts and questionnaires to patients and orthopaedic surgeons. Patient-reported instability and function were obtained via questionnaires and compared between patients with non-ACLR and ACLR treatment decisions. The ACLR treatment group was classified retrospectively by decision phase: acute phase (decision made between injury day and 31 days after injury), subacute phase (decision made between 32 days and up to 5 months after injury), and late phase (decision made 5-12 months after injury). Data were evaluated using descriptive statistics, and group comparisons were made using parametric or nonparametric tests as appropriate. Results: The main reasons for a non-ACLR treatment decision were no knee instability and no problems with knee function. The main reasons for an ACLR treatment decision were high activity demands and knee instability. Patients in the non-ACLR group were significantly older ( P = .031) and had a lower preinjury activity level than did those in the acute-phase ( P < .01) and subacute-phase ( P = .006) ACLR decision groups. There were no differences in patient-reported instability and function between treatment decision groups at baseline, 4 weeks after injury, or 3 months after injury. Conclusion: Activity demands, not patient-reported knee instability, may be the most important factor in the decision-making process for treatment after ACL injury. We suggest a decision-making algorithm for patients with ACL injuries and no high activity demands; waiting for >3 months can help distinguish those who need surgical intervention from those who can undergo nonoperative management. Registration: NCT02931084 ( ClinicalTrials.gov identifier).

Downregulation of B lymphocyte stimulator expression by curcumin in B lymphocyte via suppressing nuclear translocation of NF-κB

2011 ◽  
Vol 650 (1) ◽  
pp. 451-457 ◽  
Author(s):  
Gang Huang ◽  
Yanchun Yang ◽  
Zhizhen Xu ◽  
Peng Zhou ◽  
Wei Gong ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Nuclear Translocation ◽  
B Lymphocyte Stimulator

scholarly journals Terapia biológica en enfermedades reumatológicas

2013 ◽  
Vol 24 (2) ◽  
pp. 141 ◽  
Author(s):  
Manuel F. Ugarte-Gil ◽  
Eduardo M. Acevedo-Vásquez ◽  
Graciela S. Alarcón
Keyword(s):  
T Lymphocyte ◽  
B Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Lymphocyte Antigen ◽  
Receptor Activator ◽  
B Lymphocyte Stimulator

El advenimiento del uso de terapias biológicas en Reumatología ha modificado significativamente el pronóstico de pacientes portadores de artritis reumatoide (AR), artritis juvenil (AJ), espondilitis anquilosante (EA), entre otras enfermedades. A diferencia de las terapias convencionales estos productos biológicos se dirigen a los llamados blancos terapéuticos ya sea estas una línea celular, un mediador inflamatorio o un receptor de superficie. Estos compuestos son producidos por células vivas mediante la tecnología del ADN recombinante. Estos compuestos pueden tener componentes humano y animal [quiméricos (Xi), humanizados (Zu)], o completamente humanos (H) lo cual se reconoce por las letras que se incluyen en el nombre de cada uno. En el campo de la Reumatología, el primer compuesto utilizado fue el etanercept (anti-factor de necrosis tumoral o anti-TNF) aprobado en 1998, pero otros anti-TNF han demostrado su beneficio en AR, como en EA y AJ. Los inhibidores de Interleucina (IL-1) casi no se usan en AR actualmente, pero si los inhibidores de IL-6, así como los agentes contra las células B y los agonistas de CTLA-4 (Cytotoxic T lymphocyte antigen). Existe asimismo un compuesto dirigido al BLyS (B-lymphocyte stimulator) el cual se usa en lupus eritematoso sistémico y otro dirigido al receptor activador del factor nuclear κB (RANKL, receptor activator of nuclear factor-κB ligand) que se usa en osteoporosis. Con el avance en el conocimiento de la patogenia de las enfermedades reumáticas, se vienen reconociendo otra blancos terapéuticas. En los años venideros, este campo ha de expandirse en proporciones geométricas.

scholarly journals The gene encoding the B-cell activating factor and B-lymphocyte stimulator (BAFF/BLyS), TNFSF13B, is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
B Lymphocyte ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
B Cell Activating Factor ◽  
Bowel Diseases ◽  
B Lymphocyte Stimulator ◽  
Inflammatory Bowel ◽  
Disease Analysis

Inflammatory bowel diseases (IBD) include Crohn’s Disease and Ulcerative Colitis (1). We mined published microarray data to understand how gene expression in the hematopoietic compartment of patients with Crohn’s Disease is most different from that of healthy controls (2-4). Across two datasets (2, 3), we found that BAFF, also known as the B-lymphocyte stimulator (BLyS), encoded by the gene TNFSF13B (5), was differentially expressed in the blood of patients with Crohn’s Disease . Analysis of a third dataset (4) revealed that BAFF was among the genes most differentially expressed in monocyte-derived macrophages from patients with Crohn’s Disease. Serum BAFF, fecal BAFF, and BAFF expression in the intestinal mucosa has been demonstrated to be increased in patients with IBD (6, 7). We show here that expression of BAFF in the peripheral blood of patients with Crohn’s Disease is also increased.

scholarly journals Attenuation of Apoptosis Underlies B Lymphocyte Stimulator Enhancement of Humoral Immune Response

2000 ◽  
Vol 192 (7) ◽  
pp. 953-964 ◽  
Author(s):  
Richard K.G. Do ◽  
Eunice Hatada ◽  
Hayyoung Lee ◽  
Michelle R. Tourigny ◽  
David Hilbert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
B Lymphocyte ◽  
Humoral Immune ◽  
B Cell Survival ◽  
B Lymphocyte Stimulator

B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.

scholarly journals Attainment of treat-to-target endpoints in SLE patients with high disease activity in the atacicept phase 2b ADDRESS II study

Rheumatology ◽  
2020 ◽  
Vol 59 (10) ◽  
pp. 2930-2938 ◽  
Author(s):  
Eric F Morand ◽  
David A Isenberg ◽  
Daniel J Wallace ◽  
Amy H Kao ◽  
Cristina Vazquez-Mateo ◽  
...  
Keyword(s):  
Disease Activity ◽  
B Lymphocyte ◽  
High Disease Activity ◽  
Treat To Target ◽  
Low Disease Activity ◽  
Post Hoc Analysis ◽  
Disease Outcomes ◽  
B Lymphocyte Stimulator ◽  
Activity State ◽  
Post Hoc

Abstract Objective Low disease activity (LDA) and remission are emerging treat-to-target (T2T) endpoints in SLE. However, the rates at which these endpoints are met in patients with high disease activity (HDA) are unknown. Atacicept, which targets B lymphocyte stimulator and a proliferation-inducing ligand, improved disease outcomes in SLE patients with HDA (SLEDAI-2K ≥10) at baseline in the phase 2b ADDRESS II study. This is a post hoc analysis of T2T endpoints in these patients. Methods Patients received weekly atacicept (75 or 150 mg s.c.) or placebo for 24 weeks (1:1:1 randomization). Attainment of three T2T endpoints, LDA (SLEDAI-2K ≤ 2), Lupus Low Disease Activity State (LLDAS) and remission (clinical SLEDAI-2K = 0, prednisone-equivalent ≤5mg/day and Physician’s Global Assessment &lt;0.5), was assessed and compared with SLE Responder Index (SRI)-4 and SRI-6 response. Results Of 306 randomized patients, 158 (51.6%) had baseline HDA. At week 24, 37 (23.4%) HDA patients attained LDA, 25 (15.8%) LLDAS and 17 (10.8%) remission. Each of these endpoints was more stringent than SRI-4 (n = 87; 55.1%) and SRI-6 (n = 67; 42.4%). Compared with placebo (n = 52), at week 24, patients treated with atacicept 150 mg (n = 51) were more likely to attain LDA [odds ratio (OR) 3.82 (95% CI: 1.44, 10.15), P = 0.007], LLDAS [OR 5.03 (95% CI: 1.32, 19.06), P = 0.018] or remission [OR 3.98 (95% CI: 0.78, 20.15), P = 0.095]. Conclusion At week 24, LDA, LLDAS and remission were more stringent than SRI-4 and SRI-6 response, were attainable in the HDA population and discriminated between treatment with atacicept 150 mg and placebo. These results suggest that T2T endpoints are robust outcome measures in SLE clinical trials and support further evaluation of atacicept in SLE. Trail registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01972568.

scholarly journals B lymphocyte stimulator: a new target for treating B cell malignancies

2008 ◽  
Vol 121 (14) ◽  
pp. 1319-1323 ◽  
Author(s):  
Jian SUN ◽  
Zhou LIN ◽  
Yan LI ◽  
Bei-fen SHEN
Keyword(s):  
B Cell ◽  
B Lymphocyte ◽  
B Cell Malignancies ◽  
B Lymphocyte Stimulator
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