scholarly journals Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjogren's syndrome and systemic lupus erythematosus

2007 ◽  
Vol 66 (6) ◽  
pp. 790-797 ◽  
Author(s):  
J. Sellam ◽  
C. Miceli-Richard ◽  
J.-E. Gottenberg ◽  
M. Ittah ◽  
F. Lavie ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Primary Sjögren’S Syndrome ◽  
Receptor Expression ◽  
Systemic Lupus ◽  
Primary Sjogren’S Syndrome ◽  
Peripheral Lymphocytes ◽  
B Cell Activating Factor

Urinary B-cell-activating factor of the tumour necrosis factor family (BAFF) in systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2029-2040 ◽  
Author(s):  
F B Vincent ◽  
R Kandane-Rathnayake ◽  
A Y Hoi ◽  
L Slavin ◽  
J D Godsell ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Renal Disease ◽  
Disease Activity ◽  
B Cell ◽  
Tumour Necrosis Factor ◽  
Lupus Erythematosus ◽  
Tumour Necrosis ◽  
Systemic Lupus ◽  
B Cell Activating Factor ◽  
Necrosis Factor

Introduction We examined the clinical relevance of urinary concentrations of B-cell–activating factor of the tumour necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) in systemic lupus erythematosus (SLE). Methods We quantified urinary BAFF (uBAFF) by enzyme-linked immunosorbent assay in 85 SLE, 28 primary Sjögren syndrome (pSS), 40 immunoglobulin A nephropathy (IgAN) patients and 36 healthy controls (HCs). Urinary APRIL (uAPRIL) and monocyte chemoattractant protein 1 (uMCP-1) were also quantified. Overall and renal SLE disease activity were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000. Results uBAFF was detected in 12% (10/85) of SLE patients, but was undetectable in HCs, IgAN and pSS patients. uBAFF was detectable in 28% (5/18) of SLE patients with active nephritis vs 5/67 (7%) of those without ( p = 0.03), and uBAFF was significantly higher in active renal patients ( p = 0.02) and more likely to be detected in patients with persistently active renal disease. In comparison, uAPRIL and uMCP-1 were detected in 32% (25/77) and 46% (22/48) of SLE patients, respectively. While no difference in proportion of samples with detectable uAPRIL was observed between SLE, HCs and IgAN patients, both uAPRIL and uMCP-1 were significantly detectable in higher proportions of patients with active renal disease. Conclusions uBAFF was detectable in a small but a significant proportion of SLE patients but not in other groups tested, and was higher in SLE patients with active renal disease.

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 AB0283 CHOREOATHETHOSIS AND LONGITUDINALLY EXTENSIVE TRANSVERSE MYELITIS AS RARE AND SEVERE MANIFESTATIONS OF NEUROPSYCHIATRIC SYSTEMIC LUPUS ERYTHEMATOSUS AND PRIMARY SJÖGREN’S SYNDROME – A TWO-CENTER EXPERIENCE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1167.2-1168
Author(s):  
P. Korsten ◽  
M. Plüß ◽  
S. Glaubitz ◽  
A. Jambus ◽  
R. Vasko ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Complete Remission ◽  
Lupus Erythematosus ◽  
Transverse Myelitis ◽  
Primary Sjögren’S Syndrome ◽  
Longitudinally Extensive Transverse Myelitis ◽  
Systemic Lupus ◽  
Primary Sjogren’S Syndrome ◽  
Life Threatening ◽  
Extensive Transverse Myelitis

Background:Systemic lupus erythematosus (SLE) can affect almost any organ system. Nevertheless, Lupus nephritis and neuropsychiatric manifestations (NPSLE) are associated with increased mortality (1). Therapeutic options include glucocorticoids, often pulse methylprednisolone (MP), and other immunosuppressive therapies. In refractory cases, therapeutic plasma exchange, rituximab, or intravenous immunoglobulins are often used (2). However, an optimal therapeutic strategy has not been established because NPSLE is an exclusion criterion in most clinical trials. In addition, NPSLE can present with a broad spectrum of manifestations ranging from cognitive dysfunction to severe and life-threatening disease with choreoathetosis or transverse myelitis (TM). In primary Sjögren’s syndrome (pSS), neurological manifestations most often include peripheral neuropathies, but TM has also been reported.Objectives:To analyze the clinical presentation and outcomes after treatment in severe, life-threatening NPSLE.Methods:We retrospectively analyzed clinical, laboratory, and imaging features in severe NPSLE manifestations in SLE and pSS patients at two tertiary academic centers (University Medical Center Göttingen, Germany, and ASST Spedali Civili Brescia, Italy) with a high volume of SLE patients. Severe NPSLE was defined as either severe movement disorder or extensive tetra- or paraplegia secondary to (longitudinally extensive) transverse myelitis.Results:Our retrospective chart review resulted in seven patients fulfilling the inclusion criteria (six with SLE and 1 with pSS). Of these, five were females (71.4%). Median age was 26 (16-55) years. Three were of Asian origin, four were of European descent. Median disease duration was 15 (2-228) months. Three patients presented with severe choreoathetosis, all had positive ANA, anti-dsDNA antibodies (abs), and complement consumption. Of note, all three had at least one positive antiphospholipid antibody (APLA). All patients received IV MP 1g x 3 and mycophenolate mofetil and achieved complete remission. Of the four patients with longitudinally extensive TM, all were ANA positive, only two had anti-dsDNA abs. None of them had APLA, and only one tested positive for anti-aquaporine-4 abs. Of all patients, only one had positive ribosomal P-abs. Patients with TM received IV MP 1g x 5 and either RTX (4 cycles with 375 mg/m2 or IVIg 0.4 g/kg/d x 5). All four TM patients improved; two improved markedly, two only moderately with residual deficits as assessed by EDMUS-grading scale and functional independence measure.Conclusion:Severe NPSLE, defined as choreoathetosis or TM require intensive treatment. While the former patients achieved complete remission, two of four patients with TM only achieved partial remission. Our data support the use of early and aggressive immunosuppressive therapy. Nevertheless, therapy for TM in the context remains insufficient and should be assessed in a controlled clinical trial setting.References:[1]Monahan RC, et al. Mortality in patients with systemic lupus erythematosus and neuropsychiatric involvement: A retrospective analysis from a tertiary referral center in the Netherlands. Lupus. 2020 Dec;29(14):1892–901.[2]Papachristos DA, et al. Management of inflammatory neurologic and psychiatric manifestations of systemic lupus erythematosus: A systematic review. Semin Arthritis Rheum. 2020 Dec 17;51(1):49–71.Disclosure of Interests:PETER KORSTEN Consultant of: PK has received honoraria by Abbvie, Bristol-Myers-Squibb, Chugai, Gilead, Glaxo Smith Kline, Janssen-Cilag, Pfizer, and Sanofi-Aventis, all unrelated to this study., Grant/research support from: PK has received research grants from GSK, unrelated to this study., Marlene Plüß: None declared, Stefanie Glaubitz: None declared, Ala Jambus: None declared, Radovan Vasko: None declared, Bettina Meike Göricke: None declared, Silvia Piantoni: None declared

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