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.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

Anticytokine therapy in systemic lupus erythematosus

Lupus ◽  
2010 ◽  
Vol 19 (12) ◽  
pp. 1460-1467 ◽  
Author(s):  
D-H. Yoo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Animal Studies ◽  
Immune Cell ◽  
Cell Types ◽  
Systemic Lupus ◽  
B Cell Activating Factor ◽  
Number Of Patients

Systemic lupus erythematosus is a prototype of heterogeneous autoimmune disease. There have been few newly approved therapeutic agents in lupus treatment for many reasons. Several animal studies and human data have shown that many potential cytokines are related to the pathogenesis and disease activity of systemic lupus erythematosus. Cytokines are produced by many immune cell types and have variable functions in the immune system. Following the success of biological agents in the treatment of inflammatory arthritis, inflammatory bowel disease, and psoriasis, biological targeting to specific cytokines or receptor molecules is now promising in the treatment of systemic lupus erythematosus. In addition to B-cell deleting modalities, clinical trials targeting potential cytokines associated with disease pathogenesis are underway at various clinical stages. Among potential cytokines, targeting agents against B-cell activating factor and interferon-alpha are in the most advanced stage, and belimumab (anti-B-cell activating factor antibody) could be the first biological agent approved in the treatment of systemic lupus erythematosus. Anti-tumor necrosis factor was tried with some success, but with a potential risk of infection in a small number of patients. In this review, we discuss the rationale for anticytokine therapies and review agents currently in clinical trials, and those that could be developed in the near future for systemic lupus erythematosus. We present the results mostly from published trials and data from http://clinicaltrials.gov/ct2/

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 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 Systemic lupus erythematosus: state of the art on clinical practice guidelines

RMD Open ◽  
2018 ◽  
Vol 4 (Suppl 1) ◽  
pp. e000793 ◽  
Author(s):  
Farah Tamirou ◽  
Laurent Arnaud ◽  
Rosaria Talarico ◽  
Carlo Alberto Scirè ◽  
Tobias Alexander ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Practice ◽  
Disease Management ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Lupus Erythematosus ◽  
Unmet Needs ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Systemic Lupus

Systemic lupus erythematosus (SLE) is the paradigm of systemic autoimmune diseases characterised by a wide spectrum of clinical manifestations with an unpredictable relapsing-remitting course. The aim of the present work was to identify current available clinical practice guidelines (CPGs) for SLE, to provide their review and to identify physicians’ and patients’ unmet needs. Twenty-three original guidelines published between 2004 and 2017 were identified. Many aspects of disease management are covered, including global disease management, lupus nephritis and neuropsychiatric involvement, management of pregnancies, vaccinations and comorbidities monitoring. Unmet needs relate with disease management of some clinical manifestations and adherence to treatment. Many patient’s unmet needs have been identified starting with faster diagnosis, need for more therapeutic options, guidelines on lifestyle issues, attention to quality of life and adequate education.

Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus

Lupus ◽  
2015 ◽  
Vol 25 (6) ◽  
pp. 582-592 ◽  
Author(s):  
D C Salazar-Camarena ◽  
P C Ortiz-Lazareno ◽  
A Cruz ◽  
E Oregon-Romero ◽  
J R Machado-Contreras ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Serum Levels ◽  
Systemic Lupus ◽  
B Cell Subsets

scholarly journals Respiratory Manifestations in Systemic Lupus Erythematosus

2021 ◽  
Vol 14 (3) ◽  
pp. 276
Author(s):  
Salvatore Di Bartolomeo ◽  
Alessia Alunno ◽  
Francesco Carubbi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Specific Pattern ◽  
Systemic Autoimmune Disease ◽  
Therapeutic Approaches ◽  
Systemic Lupus ◽  
Respiratory Involvement ◽  
Life Threatening

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by a wide spectrum of clinical manifestations. The respiratory system can be involved in up to 50–70% of patients and be the presenting manifestation of the disease in 4–5% of cases. Every part of the respiratory part can be involved, and the severity can vary from mild self-limiting to life threatening forms. Respiratory involvement can be primary (caused by SLE itself) or secondary (e.g., infections or drug toxicity), acute or chronic. The course, treatment and prognosis vary greatly depending on the specific pattern of the disease. This review article aims at providing an overview of respiratory manifestations in SLE along with an update about therapeutic approaches including novel biologic therapies.

Sign in / Sign up

Export Citation Format

Share Document