scholarly journals Phenotyping of P105-Negative B Cell Subsets in Patients with Systemic Lupus Erythematosus

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Syuichi Koarada ◽  
Yoshifumi Tada ◽  
Rie Suematsu ◽  
Sachiko Soejima ◽  
Hisako Inoue ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Normal Subjects ◽  
Systemic Lupus ◽  
Phenotypic Analysis ◽  
B Cell Subsets

This study aimed to investigate phenotype of RP105(−) B cell subsets in patients with systemic lupus erythematosus (SLE). Flow cytometry was used for phenotyping RP105-negaive B cell subsets. Based on CD19, RP105, and CD138 expression, RP105(−) B cells consist of at least 5 subsets of late B cells, including CD19(+)RP105(int), CD19(+) RP105(−), CD19(low) RP105(−) CD138(−), CD19(low) RP105(−)CD138(int), and CD19(low) RP105(−) CD138(++) B cells. Especially, CD19(+)RP105(int) and CD19(low) RP105(−)CD138(int) B cells are significantly larger than other RP105(−) B cell subsets in SLE. By comparison of RP105(−) B cell subsets between patients with SLE and normal subjects, these subsets were detectable even in normal subjects, but the percentages of RP105(−) B cell subsets were significantly larger in SLE. The phenotypic analysis of RP105(−) B cell subsets suggests dysregulation of later B cell subsets in SLE and may provide new insights into understanding regulation of B cells in human SLE.

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

scholarly journals Multiple Functions of B Cells in the Pathogenesis of Systemic Lupus Erythematosus

2019 ◽  
Vol 20 (23) ◽  
pp. 6021 ◽  
Author(s):  
Kongyang Ma ◽  
Wenhan Du ◽  
Xiaohui Wang ◽  
Shiwen Yuan ◽  
Xiaoyan Cai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Therapeutic Interventions ◽  
Systemic Lupus ◽  
Autoantibody Production ◽  
Regulatory B Cell ◽  
Functional Features ◽  
B Cell Subsets

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production and multi-organ involvement. Although the etiology of SLE still remains unclear, recent studies have characterized several pathogenic B cell subsets and regulatory B cell subsets involved in the pathogenesis of SLE. Among pathogenic B cell subsets, age-associated B cells (ABCs) are a newly identified subset of autoreactive B cells with T-bet-dependent transcriptional programs and unique functional features in SLE. Accumulation of T-bet+ CD11c+ ABCs has been observed in SLE patients and lupus mouse models. In addition, innate-like B cells with the autoreactive B cell receptor (BCR) expression and long-lived plasma cells with persistent autoantibody production contribute to the development of SLE. Moreover, several regulatory B cell subsets with immune suppressive functions have been identified, while the impaired inhibitory effects of regulatory B cells have been indicated in SLE. Thus, further elucidation on the functional features of B cell subsets will provide new insights in understanding lupus pathogenesis and lead to novel therapeutic interventions in the treatment of SLE.

Differential effects of epratuzumab on peripheral blood B cells of patients with systemic lupus erythematosus versus normal controls

2007 ◽  
Vol 67 (4) ◽  
pp. 450-457 ◽  
Author(s):  
A M Jacobi ◽  
D M Goldenberg ◽  
F Hiepe ◽  
A Radbruch ◽  
G R Burmester ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Peripheral Blood ◽  
Therapeutic Option ◽  
Normal Subjects ◽  
Systemic Lupus

Objective:B lymphocytes have been implicated in the pathogenesis of lupus and other autoimmune diseases, resulting in the introduction of B cell-directed therapies. Epratuzumab, a humanised anti-CD22 monoclonal antibody, is currently in clinical trials, although its effects on patients’ B cells are not completely understood.Methods:This study analysed the in vivo effect of epratuzumab on peripheral B cell subsets in 12 patients with systemic lupus erythematosus, and also addressed the in vitro effects of the drug by analysing anti-immunoglobulin-induced proliferation of isolated B cells obtained from the peripheral blood of 11 additional patients with lupus and seven normal subjects.Results:Upon treatment, a pronounced reduction of CD27– B cells and CD22 surface expression on CD27– B cells was observed, suggesting that these cells, which mainly comprise naïve and transitional B cells, are preferentially targeted by epratuzumab in vivo. The results of in vitro studies indicate additional regulatory effects of the drug by reducing the enhanced activation and proliferation of anti-immunoglobulin-stimulated lupus B cells after co-incubation with CD40L or CpG. Epratuzumab inhibited the proliferation of B cells from patients with systemic lupus erythematosus but not normal B cells under all culture conditions.Conclusions:Epratuzumab preferentially modulates the exaggerated activation and proliferation of B cells from patients with lupus in contrast to normal subjects, thus suggesting that epratuzumab might offer a new therapeutic option for patients with systemic lupus erythematosus, as enhanced B cell activation is a hallmark of this disease.

Flow Cytometry Signature for Kikuchi-Fujimoto/Lupus Lymphadenitis Derived From 975 Benign and Malignant Lymphadenopathies

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S105-S106
Author(s):  
Jyoti Kumar ◽  
Gregory Scott ◽  
Jean Oak ◽  
Philipp Raess ◽  
Dita Gratzinger
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Patient Age ◽  
T Cell Lymphomas ◽  
Patient Âgé

Abstract Introduction Kikuchi lymphadenitis is a benign disease with histologic features that can be challenging to discern from malignant or infectious diagnoses. Furthermore, Kikuchi lymphadenitis and systemic lupus erythematosus–associated lymphadenitis (KD/SLE) show overlapping histologic features. We used flow cytometry to evaluate if KD/SLE has a distinct immunophenotype from other lymphadenopathies. Methods and Materials Sixteen cases of KD/SLE were compared to 959 control cases at Stanford by flow cytometry for three scenarios: KD/SLE versus T-cell lymphomas, all benign cases, and all benign and malignant cases. Select cases of KD/SLE and benign lymph nodes were analyzed by immunohistochemistry to evaluate the B-cell characteristics. A test set of five KD cases were compared to five normal controls from an independent institution to evaluate cross-platform reproducibility of the KD/SLE flow cytometry signature. Results The most discriminatory signature for KD/SLE versus all other benign cases comprised two surface antigen pairs (high CD38+ CD19+, low large-cell CD57+ CD3+), patient age, lymph node location, and four additional flow antigens (100% sensitivity, 99.6% specificity). The signature for KD/SLE versus T-cell lymphomas consisted of two flow antigens (high CD38+ CD19+ and high CD3) and patient age (100% sensitivity, 100% specificity). Based on the flow data, immunohistochemistry was performed to evaluate the B-cell characteristics. We observed clusters of IgD-positive B cells surrounding activated T-cell foci without IgM expression, suggesting that these cells represent either naive cells or memory IgD-positive B cells. Flow cytometry showed increased CD23 with minimal CD5 expression, supporting the hypothesis of naive functional anergic/autoreactive IgD+ IgM– B cells. Conclusion We have identified a signature that can distinguish Kikuchi disease and systemic lupus erythematosus from a large cohort of benign and malignant entities, likely reflecting a shared stable underlying etiology of KD/SLE. Our study provides a valuable tool to enhance the ability to accurately diagnose KD/SLE.

scholarly journals The expansion of activated naive DNA autoreactive B Cells and its association with disease activity in Systemic Lupus Erythematosus patients

2021 ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of Systemic Lupus Erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients' peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis. Thus, aNAV B cells may provide a candidate biomarker for monitoring disease activity in these patients.

scholarly journals THU0044 SINGLE CELL ANALYSIS OF BONE MARROW AND PERIPHERAL ALTERED B CELL DIFFERENTIATION IN PATIENTS WITH ACTIVE SLE AND THE MECHANISM OF ABNORMAL EARLY B CELL DEVELOPMENT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 234.3-235
Author(s):  
T. Fu ◽  
Y. Yang ◽  
X. Gu ◽  
C. Dong ◽  
R. Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Cell Development ◽  
B Cell Development ◽  
B Cell Differentiation ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:B cell differentiation and dysfunction play a key role in the pathogenesis of Systemic lupus erythematosus (SLE). Bone marrow (BM) is the development organ of B cells, and also the home and residence place of plasma cells and memory B cells. However, there is a lack of studies on B cells in BM with lupus.Objectives:To map the development of BM and peripheral B cells and investigate the mechanism of abnormal early B cell development in SLE.Methods:A total of 11 SLE patients and 5 age- and sex-matched controls were recruited.BM and peripheral B cell subsets were measured by flow cytometry. sorting-purified B cell subsets were subject toSingle-cell RNA sequencing (scRNA-seq) and functional studies. Plasma cytokines and secreted immunoglobulins were detected by Luminex or ELISA. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI).Results:In the present study, we find out that the percentage of monocytes in MNC (p=0.070) and plasma cells(p=0.001)in CD19+ were significantly decreased in BM of SLE, compared to healthy controls. While, SLE patients had increased T%MNC(p=0.008) and B%CD19+(p=0.002) in BM that controls. In detail, the B cell subsets of bone marrow in patients with active lupus (SLEDAI≥8 score) were seriously disordered, showing the increasing T%MNC(p=0.049), propre-B%CD19+ (p=0.006)and immature B cell%CD19+ (p=0.010) than healthy donors. propre-B%CD19+ exhibited good relationship with SLEDAI. By integrating single B cell expression profiling and repertoire analysis, we map the development of B cells in BM and peripheral and pathogenic characteristics of early B cells, especially propre-B.Conclusion:These findings demonstrated that early B cells in BM, especially propre-B are abnormally differentiated with dysregulations. BM is an important organ targeted by SLE. This studyis not only to clarify the internal mechanism of the disorder of differentiation of B cells, but also to provide new clues for the targeted diagnosis and treatment of SLE.References:[1]Palanichamy, A., et al.,Neutrophil-mediated IFN activation in the bone marrow alters B cell development in human and murine systemic lupus erythematosus.J Immunol, 2014.192(3): p. 906-18.[2]Papadaki, H.A., J.C. Marsh, and G.D. Eliopoulos,Bone marrow stem cells and stromal cells in autoimmune cytopenias.Leuk Lymphoma, 2002.43(4): p. 753-60.[3]Karrar, S. and D.S. Cunninghame Graham,Abnormal B Cell Development in Systemic Lupus Erythematosus: What the Genetics Tell Us.Arthritis Rheumatol, 2018.70(4): p. 496-507.[4]Woods, M., Y.R. Zou, and A. Davidson,Defects in Germinal Center Selection in SLE.Front Immunol, 2015.6: p. 425.[5]Upregulation of p16INK4A promotes cellular senescence of bone marrow-derived mesenchymal stem cells from systemic lupus erythematosus patients.Cell Signal, 2012.24(12): p. 2307-14.Disclosure of Interests:None declared

scholarly journals POS0680 BELIMUMAB ADD-ON THERAPY MOBILISES MEMORY B CELLS INTO THE CIRCULATION OF PATIENTS WITH SLE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 585.1-585
Author(s):  
E. J. Arends ◽  
M. Zlei ◽  
C. M. Tipton ◽  
Z. Osmani ◽  
S. Kamerling ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Memory B Cells ◽  
Lymphocyte Trafficking ◽  
Systemic Lupus ◽  
Research Support

Background:Belimumab (BLM), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with active severe systemic lupus erythematosus (SLE) and lupus nephritis (LN). There is clinical evidence that combining BLM with B cell depleting therapy can ameliorate disease activity in severe, refractory SLE patients1. Although BLM is a B cell directed therapy and has been shown to significantly decrease total B cells, flow cytometry observations suggest a rapid increase of circulating memory B cells (MBC)2.Objectives:To investigate dynamics of B-cell subsets in SLE patients treated with or without BLM, with a focus on assessing MBC characteristics.Methods:Extensive B cell subset phenotyping was performed by high-sensitivity (HS) flow cytometry (acquisition of 107 leukocytes; per EuroFlow protocols3) on samples from active LN or SLE patients with major organ involvement treated with standard of care (SOC) consisting of high dose steroids and mycophenolate mofetil combined with or without the addition of BLM. MBC gene expression profiles were characterized with single-cell RNA and V(D)J sequencing (ScRNA-SEQ).Results:By employing HS flowcytometry, we established that the absolute increase in circulating MBC in SLE and LN patients was significant for patients who initiated BLM (Figure 1). The increase was observed in a broad range of MBC subsets (Unswitched, IgG1+, IgG2+, IgA1+, IgA2+) at 2 and 4 weeks following initiation of BLM treatment. This rise in MBC could hypothetically be attributed to either proliferation of blood MBC, BLM induced migration of tissue-resident MBCs or BLM related retention of tissue-destined MBC in the blood. ScRNA-SEQ analysis of cell cycle gene-expression was performed and established in both groups a non-proliferating phenotype [in approximately ~94%] of MBC post-treatment, including absence of MKI67 as active proliferation marker. Clonal diversity analysis comparing week 2 with baseline revealed an unexpected decrease of the largest MBC clones in BLM, whereas no change in clonality was observed with SOC alone. Together these data indicate that proliferation is unlikely to be responsible for the observed increase in MBC by BLM. Furthermore, a clear difference was found in gene-expression levels between both treatment groups: BLM was responsible for the upregulation of 72 vs 10 genes in SOC, likewise 162 vs 32 genes were downregulated. Most importantly, a significant downregulation of the migration genes SELL (CD62L), CCR7, ITGB1, RAC2 and ICAM2, were specifically seen in BLM treated patients. This may reflect disrupted lymphocyte trafficking, preventing MBCs from transmigrating from the blood into tissue owing to reduced migration molecules, or preventing MBCs from being retained at the tissue level owing to reduction in tissue adhesion proteins.Conclusion:The addition of BLM to SOC significantly increases MBCs in patients with SLE independently of proliferation, accompanied by a strong modulation of gene expression, including reduced expression of migration markers pointing towards disrupted lymphocyte trafficking. These data may have important implications for improving treatment strategies in patients with LN or severe SLE, as a deeper depletion of autoreactive MBCs could be established by adding B-cell-depleting therapy after the initiation of BLM.Figure 1.Change in pre-germinal center and memory B cell counts from baseline to week 4 of patients with SLE or LN treated with SOC (n=8) or SOC+BLM (n=11).References:[1]Arends EJ et al. Long-term effects of combined B cell immunomodulation with rituximab and belimumab in severe, refractory systemic lupus erythematosus: 2-year results. Nephrol Dial Transplant. 2020 Jun 27 gfaa117.[2]Stohl W et al. Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with SLE. Arthritis Rheum. 2012;64(7):2328-2337.[3]Blanco et al, Age-associated distribution of B and plasma cell subsets in peripheral blood - J Allergy Clin Immunol 2018 141 2208-2219.Disclosure of Interests:Eline J. Arends: None declared, Mihaela Zlei: None declared, Christopher M. Tipton: None declared, Zgjim Osmani: None declared, Sylvia Kamerling: None declared, Ton Rabelink: None declared, Ignacio Sanz: None declared, Jacques J.M. van Dongen Paid instructor for: BD Biosciences: Educational Services (fees for LUMC), Consultant of: BD Biosciences and Cytognos (fees for LUMC), Grant/research support from: GSK (flow cytometry studies for GSK BLISS-BELIEVE study NCT03312907), Cees van Kooten: None declared, Y.K. Onno Teng Consultant of: Aurinia provided financial compensation for consultancy, Grant/research support from: GSK provided belimumab for free for the Synbiose-2 clinical trial and provided an unrestricted grant to conduct the study.

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