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

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.

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.

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 Genetic and physical interaction of the B-cell systemic lupus erythematosus-associated genes BANK1 and BLK

2011 ◽  
Vol 71 (1) ◽  
pp. 136-142 ◽  
Author(s):  
Casimiro Castillejo-López ◽  
Angélica M Delgado-Vega ◽  
Jerome Wojcik ◽  
Sergey V Kozyrev ◽  
Elangovan Thavathiru ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Genetic Interaction ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Genetic Interactions ◽  
Physical Interaction ◽  
Systemic Lupus ◽  
Src Tyrosine Kinase

ObjectivesAltered signalling in B cells is a predominant feature of systemic lupus erythematosus (SLE). The genes BANK1 and BLK were recently described as associated with SLE. BANK1 codes for a B-cell-specific cytoplasmic protein involved in B-cell receptor signalling and BLK codes for an Src tyrosine kinase with important roles in B-cell development. To characterise the role of BANK1 and BLK in SLE, a genetic interaction analysis was performed hypothesising that genetic interactions could reveal functional pathways relevant to disease pathogenesis.MethodsThe GPAT16 method was used to analyse the gene–gene interactions of BANK1 and BLK. Confocal microscopy was used to investigate co-localisation, and immunoprecipitation was used to verify the physical interaction of BANK1 and BLK.ResultsEpistatic interactions between BANK1 and BLK polymorphisms associated with SLE were observed in a discovery set of 279 patients and 515 controls from northern Europe. A meta-analysis with 4399 European individuals confirmed the genetic interactions between BANK1 and BLK. As BANK1 was identified as a binding partner of the Src tyrosine kinase LYN, the possibility that BANK1 and BLK could also show a protein–protein interaction was tested. The co-immunoprecipitation and co-localisation of BLK and BANK1 were demonstrated. In a Daudi cell line and primary naive B cells endogenous binding was enhanced upon B-cell receptor stimulation using anti-IgM antibodies.ConclusionThis study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. The results have important consequences for the understanding of SLE and other autoimmune diseases and identify a potential new signalling pathway.

Clinical case of lung lesions in patient with newly diagnosed systemic lupus erythematosus

2019 ◽  
Vol 1 (9) ◽  
pp. 53-57
Author(s):  
T. N. Gavva ◽  
L. V. Kuzmenkova ◽  
Yu. N. Fedulaev ◽  
T. V. Pinchuk ◽  
D. D. Kaminer ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Case ◽  
Clinical Manifestations ◽  
Lung Damage ◽  
Newly Diagnosed ◽  
Systemic Lupus ◽  
Lung Lesions ◽  
Laboratory Parameters ◽  
Clinical Interest

A case of lung damage in systemic lupus erythematosus (SLE) in a 33-year-old woman is described. This case is of clinical interest due to the complexity of diagnosis due to the fact that SLE is a disease with diverse clinical manifestations involving many organs and systems, which often makes it difficult to timely recognize the onset of the disease. SLE still remains a challenge and requires special attention to the patient s history, clinical and laboratory parameters of the patient, as well as specific immunological examinations.

THE CLINICAL, LABORATORY MANIFESTATIONS AND HISTOPATHOLOGY IN NEPHROTIC PATIENTS WITH LUPUS NEPHRITIS

2018 ◽  
pp. 52-58
Author(s):  
Le Thuan Nguyen ◽  
Bui Bao Hoang
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Clinical Laboratory ◽  
Activity Index ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Cross Sectional ◽  
Organ Systems ◽  
Tubulointerstitial Lesions

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems. The kidney appears to be the most commonly affected organ, especially nephrotic is a serious kidney injury. The clinical, laboratory manifestations and histopathology are very useful for diagnosis, provide the means of predicting prognosis and guiding therapy in nephrotic patients with lupus nephritis. Methods: Descriptive cross-sectional study of nephrotic patients with lupus treated in the Department of Nephrology Trung Vuong Hospital and Cho Ray Hospital between May/2014 and May/2017. Renal histopathological lesions were classified according to International Society of Nephrology/Renal Pathology Society - ISN/RPS ’s 2003. The clinical, laboratory manifestations and histopathological features were described. Results: Of 32 LN with nephritic range proteinuria cases studied, 93.7% were women. The 3 most common clinical manifestations were edema (93.8%), hypertension (96.8%) and pallor (68.9%), musculoskeletal manifestions (46.9%), malar rash (40.6%). There was significant rise in laboratory and immunological manifestions with hematuria (78.1%), Hb < 12g/dL (93.5%), increased Cholesterol (100%), and Triglycerid (87.5%), Creatinine > 1.4 mg/dL (87.5%), increased BUN 71.9%, ANA (+) 93.8%, Anti Ds DNA(+) 96.9%, low C3: 96.9%, low C4: 84.4%. The most various and severe features were noted in class IV with active tubulointerstitial lesions and high activity index. Conclusion: Lupus nephritis with nephrotic range proteinuria has the more severity of histopathological feature and the more severity of the more systemic organ involvements and laboratory disorders were noted. Key words: Systemic lupus, erythematosus (SLE) lupus nepphritis, clinical

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