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Article ; Online: B cells in systemic lupus erythematosus.

Szelinski, Franziska / Lino, Andreia C / Dörner, Thomas

2021 Volume 34, Issue 2, Page(s) 125–132

Abstract: Purpose of review: New insight into altered B cell distribution including newly identified subsets and abnormalities in systemic lupus erythematosus (SLE) as well as their role in immune protection are summarized in this review.: Recent findings: SLE ...

Abstract	Purpose of review: New insight into altered B cell distribution including newly identified subsets and abnormalities in systemic lupus erythematosus (SLE) as well as their role in immune protection are summarized in this review. Recent findings: SLE carries characteristic B cell abnormalities, which offer new insights into B cell differentiation and their disturbances including discoveries of pathogenic B cell subsets and intrinsic B cell abnormalities. A recent study in SLE found that antigen-experienced B cell subsets lacking expression of CD27 and IgD defined by their lack of CXCR5 and CD19low expression are expanded in SLE and represent plasmablasts likely escaping proper selection. In terms of therapeutic targeting with broader coverage than rituximab, second-generation anti-CD20, anti-CD38 and CD19-CART treatment experiences have advanced our understanding recently. However, the key role of qualitative and quantitative B cell requirements in connection with T cells became apparent during SARS-Cov2 infection and vaccination, especially in patients with gradual B cell impairments by rituximab, mycophenolate mofetil and cyclophosphamide. Summary: Identification and characterization relevant B cell subsets together with altered regulatory mechanisms in SLE facilitates new approaches in targeting pathogenic B cells but require consideration of preservation of protection.
MeSH term(s)	B-Lymphocytes ; COVID-19 ; Humans ; Lupus Erythematosus, Systemic ; RNA, Viral ; SARS-CoV-2
Chemical Substances	RNA, Viral
Language	English
Publishing date	2021-12-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1045317-9
ISSN	1531-6963 ; 1040-8711
ISSN (online)	1531-6963
ISSN	1040-8711
DOI	10.1097/BOR.0000000000000865
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Article ; Online: Application of blinatumomab, a bispecific anti-CD3/CD19 T-cell engager, in treating severe systemic sclerosis: A case study.

Subklewe, Marion / Magno, Giulia / Gebhardt, Christina / Bücklein, Veit / Szelinski, Franziska / Arévalo, Héctor Julián Rincón / Hänel, Gerulf / Dörner, Thomas / Zugmaier, Gerhard / von Bergwelt-Baildon, Michael / Skapenko, Alla / Schulze-Koops, Hendrik

European journal of cancer (Oxford, England : 1990)

2024 Volume 204, Page(s) 114071

Abstract: Systemic sclerosis, a severe inflammatory autoimmune disease, shares a common thread with cancer through the underlying mechanism of inflammation. This inflammatory milieu not only drives the immune dysregulation characteristic of autoimmune diseases but ...

Abstract	Systemic sclerosis, a severe inflammatory autoimmune disease, shares a common thread with cancer through the underlying mechanism of inflammation. This inflammatory milieu not only drives the immune dysregulation characteristic of autoimmune diseases but also plays a pivotal role in the pathogenesis of cancer. Among the cellular components involved, B cells have emerged as key players in hematologic tumor and autoimmune disease, contributing to immune dysregulation and persistent tissue fibrosis in systemic sclerosis, as well as tumor progression and immune evasion in cancer. Consequently, novel therapeutic strategies targeting B cells hold promise in both conditions. Recent exploration of CD19 CAR T cells in severe systemic sclerosis patients has shown great potential, but also introduced possible risks and drawbacks associated with viral vectors, prolonged CAR T cell persistence, lengthy production timelines, high costs, and the necessity of conditioning patients with organotoxic and fertility-damaging chemotherapy. Given these challenges, alternative CD19-depleting approaches are of high interest for managing severe systemic autoimmune diseases. Here, we present the pioneering use of blinatumomab, a bispecific anti-CD3/anti-CD19 T cell engager in a patient with progressive, severe systemic sclerosis, offering a promising alternative for such challenging cases.
MeSH term(s)	Humans ; Antibodies, Bispecific/therapeutic use ; Scleroderma, Systemic/drug therapy ; Scleroderma, Systemic/immunology ; Antigens, CD19/immunology ; T-Lymphocytes/immunology ; T-Lymphocytes/drug effects ; Female ; CD3 Complex/immunology ; CD3 Complex/metabolism ; Middle Aged ; Immunotherapy, Adoptive/methods
Chemical Substances	blinatumomab ; CD19 molecule, human
Language	English
Publishing date	2024-04-22
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2024.114071
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Article ; Online: Therapeutic implications of the anergic/postactivated status of B cells in systemic lupus erythematosus.

Dörner, Thomas / Szelinski, Franziska / Lino, Andreia C / Lipsky, Peter E

RMD open

2020 Volume 6, Issue 2

Abstract: Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma cells, atypical CD27-IgD- B cells with increased CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ ... ...

Abstract	Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma cells, atypical CD27-IgD- B cells with increased CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ subsets and anergic CD11c+Tbet+ age-associated B cells. Most findings, together with preclinical lupus models, support the concept of B cell hyperactivity in SLE. However, it remains largely unknown whether these specific B cell subsets have pathogenic consequences and whether they provide relevant therapeutic targets. Recent findings indicate a global distortion of B cell functional capability, in which the entire repertoire of naïve and memory B cells in SLE exhibits an anergic or postactivated (APA) functional phenotype. The APA status of SLE B cells has some similarities to the functional derangement of lupus T cells. APA B cells are characterised by reduced global cytokine production, diminished B cell receptor (BCR) signalling with decreased Syk and Bruton's tyrosine kinase phosphorylation related to repeated in vivo BCR stimulation as well as hyporesponsiveness to toll-like receptor 9 engagement, but intact CD40 signalling. This APA status was related to constitutive co-localisation of CD22 linked to phosphatase SHP-1 and increased overall protein phosphatase activities. Notably, CD40 co-stimulation could revert this APA status and restore BCR signalling, downregulate protein tyrosine phosphatase transcription and promote B cell proliferation and differentiation. The APA status and their potential rescue by bystander help conveyed through CD40 stimulation not only provides insights into possible mechanisms of escape of autoreactive clones from negative selection but also into novel ways to target B cells therapeutically.
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Biomarkers ; CD40 Antigens/metabolism ; Cell Differentiation/immunology ; Clonal Anergy/immunology ; Disease Susceptibility ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Lupus Erythematosus, Systemic/etiology ; Lupus Erythematosus, Systemic/metabolism ; Lupus Erythematosus, Systemic/therapy ; Lymphocyte Activation/immunology ; Receptors, Antigen, B-Cell/metabolism ; Signal Transduction ; Toll-Like Receptor 9/metabolism
Chemical Substances	Biomarkers ; CD40 Antigens ; Receptors, Antigen, B-Cell ; Toll-Like Receptor 9
Language	English
Publishing date	2020-07-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2812592-7
ISSN	2056-5933 ; 2056-5933
ISSN (online)	2056-5933
ISSN	2056-5933
DOI	10.1136/rmdopen-2020-001258
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Article ; Online: Transcriptional profiling upon T cell stimulation reveals down-regulation of inflammatory pathways in T and B cells in SLE versus Sjögren's syndrome.

Kwon, Gino / Wiedemann, Annika / Steinheuer, Lisa M / Stefanski, Ana-Luisa / Szelinski, Franziska / Racek, Tomas / Frei, Andreas Philipp / Hatje, Klas / Kam-Thong, Tony / Schubert, David / Schindler, Thomas / Dörner, Thomas / Thurley, Kevin

NPJ systems biology and applications

2023 Volume 9, Issue 1, Page(s) 62

Abstract: Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific ... ...

Abstract	Systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share clinical as well as pathogenic similarities. Although previous studies suggest various abnormalities in different immune cell compartments, dedicated cell-type specific transcriptomic signatures are often masked by patient heterogeneity. Here, we performed transcriptional profiling of isolated CD4, CD8, CD16 and CD19 lymphocytes from pSS and SLE patients upon T cell stimulation, in addition to a steady-state condition directly after blood drawing, in total comprising 581 sequencing samples. T cell stimulation, which induced a pronounced inflammatory response in all four cell types, gave rise to substantial re-modulation of lymphocyte subsets in the two autoimmune diseases compared to healthy controls, far exceeding the transcriptomic differences detected at steady-state. In particular, we detected cell-type and disease-specific down-regulation of a range of pro-inflammatory cytokine and chemokine pathways. Such differences between SLE and pSS patients are instrumental for selective immune targeting by future therapies.
MeSH term(s)	Humans ; Sjogren's Syndrome/genetics ; Sjogren's Syndrome/metabolism ; T-Lymphocytes/metabolism ; Down-Regulation/genetics ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/metabolism ; Autoimmune Diseases
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ISSN	2056-7189
ISSN (online)	2056-7189
DOI	10.1038/s41540-023-00319-z
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Article ; Online: Persistent but atypical germinal center reaction among 3

Stefanski, Ana-Luisa / Rincon-Arevalo, Hector / Schrezenmeier, Eva / Karberg, Kirsten / Szelinski, Franziska / Ritter, Jacob / Chen, Yidan / Meisel, Christian / Jahrsdörfer, Bernd / Ludwig, Carolin / Schrezenmeier, Hubert / Lino, Andreia C / Dörner, Thomas

Frontiers in immunology

2022 Volume 13, Page(s) 943476

Abstract: Background: Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy ... ...

Abstract	Background: Durable vaccine-mediated immunity relies on the generation of long-lived plasma cells and memory B cells (MBCs), differentiating upon germinal center (GC) reactions. SARS-CoV-2 mRNA vaccination induces a strong GC response in healthy volunteers (HC), but limited data is available about response longevity upon rituximab treatment. Methods: We evaluated humoral and cellular responses upon 3rd vaccination in seven patients with rheumatoid arthritis (RA) who initially mounted anti-spike SARS-CoV-2 IgG antibodies after primary 2x vaccination and got re-exposed to rituximab (RTX) 1-2 months after the second vaccination. Ten patients with RA on other therapies and ten HC represented the control groups. As control for known long-lived induced immunity, we analyzed humoral and cellular tetanus toxoid (TT) immune responses in steady-state. Results: After 3 Summary: On the basis of pre-existing affinity matured MBCs within primary immunisation, RTX re-exposed patients revealed a persistent but atypical GC immune response accompanied by boosted spike-specific memory CD4 T cells upon SARS-CoV-2 recall vaccination.
MeSH term(s)	Antibodies, Viral ; Arthritis, Rheumatoid ; COVID-19 ; COVID-19 Vaccines ; Germinal Center ; Humans ; Immunoglobulin A ; Immunoglobulin G ; Rituximab ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Immunoglobulin A ; Immunoglobulin G ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2022-08-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.943476
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Article ; Online: B Cell Characteristics at Baseline Predict Vaccination Response in RTX Treated Patients.

Stefanski, Ana-Luisa / Rincon-Arevalo, Hector / Schrezenmeier, Eva / Karberg, Kirsten / Szelinski, Franziska / Ritter, Jacob / Chen, Yidan / Jahrsdörfer, Bernd / Ludwig, Carolin / Schrezenmeier, Hubert / Lino, Andreia C / Dörner, Thomas

Frontiers in immunology

2022 Volume 13, Page(s) 822885

Abstract: Background: Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and ... ...

Abstract	Background: Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients. Methods: B- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets Results: Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naïve and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders. Summary: Substantial repopulation of the naïve B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses.
MeSH term(s)	Arthritis, Rheumatoid ; COVID-19 ; Humans ; Immunoglobulin G ; Rituximab/therapeutic use ; SARS-CoV-2 ; Vaccination/methods
Chemical Substances	Immunoglobulin G ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2022-04-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.822885
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Article ; Online: Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19

Szelinski, Franziska / Stefanski, Ana Luisa / Schrezenmeier, Eva / Rincon-Arevalo, Hector / Wiedemann, Annika / Reiter, Karin / Ritter, Jacob / Lettau, Marie / Dang, Van Duc / Fuchs, Sebastian / Frei, Andreas P / Alexander, Tobias / Lino, Andreia C / Dörner, Thomas

Arthritis & rheumatology (Hoboken, N.J.)

2022 Volume 74, Issue 9, Page(s) 1556–1568

Abstract: Objective: Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD-CD27- double-negative B cell populations. Previous studies showed that double-negative B ... ...

Abstract	Objective: Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD-CD27- double-negative B cell populations. Previous studies showed that double-negative B cells represent a heterogeneous subset, and further characterization is needed. Methods: We analyzed 2 independent cohorts of healthy donors and SLE patients, using a combined approach of flow cytometry (for 16 healthy donors and 28 SLE patients) and mass cytometry (for 18 healthy donors and 24 SLE patients) and targeted RNA-Seq analysis. To compare B cell subset formation during the acute immune response versus that during autoimmune disease, we investigated healthy donors at various time points after receipt of the BNT162b2 messenger RNA COVID-19 vaccine and patients with acute SARS-CoV-2 infection, using flow cytometry. Results: We found that IgD-CD27+ switched and atypical IgD-CD27- memory B cells, the levels of which were increased in SLE patients, represented heterogeneous populations composed of 3 different subsets each. CXCR5+CD19 Conclusion: Our data suggest that CXCR5-CD19
MeSH term(s)	Antigens, CD19/genetics ; Antigens, CD19/metabolism ; B-Lymphocyte Subsets/metabolism ; BNT162 Vaccine ; COVID-19 ; COVID-19 Vaccines ; Humans ; Immunoglobulin D ; Lupus Erythematosus, Systemic/genetics ; Lupus Erythematosus, Systemic/metabolism ; Phenotype ; Receptors, CXCR5/genetics ; Receptors, CXCR5/metabolism ; SARS-CoV-2
Chemical Substances	Antigens, CD19 ; COVID-19 Vaccines ; CXCR5 protein, human ; Immunoglobulin D ; Receptors, CXCR5 ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42157
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Article ; Online: Elevated STAT1 expression but not phosphorylation in lupus B cells correlates with disease activity and increased plasmablast susceptibility.

Aue, Arman / Szelinski, Franziska / Weißenberg, Sarah Y / Wiedemann, Annika / Rose, Thomas / Lino, Andreia C / Dörner, Thomas

Rheumatology (Oxford, England)

2020 Volume 59, Issue 11, Page(s) 3435–3442

Abstract: Objectives: SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) - signal transducer and activator of ... ...

Abstract	Objectives: SLE is characterized by two pathogenic key signatures, type I IFN and B-cell abnormalities. 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). JAK-STAT inhibition is an attractive therapeutic possibility for SLE. 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 with 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), seven primary Sjögren's (pSS) and 22 SLE patients was analysed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs (peripheral blood mononuclear cells) 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. STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ. Conclusion: Enhanced expression of STAT1 by B-cell candidates as a 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 a promise to block STAT1 expression and control plasmablast induction in SLE.
MeSH term(s)	Adult ; Aged ; Arthritis, Rheumatoid/immunology ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/physiopathology ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; Case-Control Studies ; Cell Differentiation ; Female ; Humans ; Immunologic Factors/pharmacology ; In Vitro Techniques ; Interferon-alpha/pharmacology ; Interferon-gamma/pharmacology ; Janus Kinases/metabolism ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/metabolism ; Lupus Erythematosus, Systemic/physiopathology ; Male ; Middle Aged ; Monocytes/immunology ; Phosphorylation/drug effects ; Plasma Cells/immunology ; STAT1 Transcription Factor/drug effects ; STAT1 Transcription Factor/metabolism ; STAT3 Transcription Factor/drug effects ; STAT3 Transcription Factor/metabolism ; Severity of Illness Index ; Signal Transduction ; Sjogren's Syndrome/immunology ; Sjogren's Syndrome/metabolism ; Sjogren's Syndrome/physiopathology ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology ; Young Adult
Chemical Substances	Immunologic Factors ; Interferon-alpha ; STAT1 Transcription Factor ; STAT1 protein, human ; STAT3 Transcription Factor ; STAT3 protein, human ; Interferon-gamma (82115-62-6) ; Janus Kinases (EC 2.7.10.2)
Language	English
Publishing date	2020-05-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keaa187
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Conference proceedings: Enrichment of phospholipid-reactive B cells among atypical memory subsets in APS patients

Nitschke, Eduard / Schrezenmeier, Eva V. / Stefanski, Ana-Luisa / Alexander, Tobias / Chen, Yidan / Dörner, Thomas / Dang, Van Duc / Rincon-Arevalo, Hector / Ritter, Jacob Casimir / Gonzalez, Jose-Bernardino / Szelinski, Franziska / Le, Tuan Anh / Lino, Andreia / Glenzer, Annika

2023 , Page(s) ET.26

Event/congress	Deutscher Rheumatologiekongress 2023, 51. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 37. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 33. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR); Leipzig; ; Gesellschaft für Kinder- und Jugendrheumatologie; 2023
Keywords	Medizin, Gesundheit
Publishing date	2023-08-30
Publisher	German Medical Science GMS Publishing House; Düsseldorf
Document type	Conference proceedings
DOI	10.3205/23dgrh045
Database	German Medical Science

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Article ; Online: CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus.

Dang, Van Duc / Mohr, Elodie / Szelinski, Franziska / Le, Tuan Anh / Ritter, Jacob / Hinnenthal, Timo / Stefanski, Ana-Luisa / Schrezenmeier, Eva / Ocvirk, Soeren / Hipfl, Christian / Hardt, Sebastian / Cheng, Qingyu / Hiepe, Falk / Löhning, Max / Dörner, Thomas / Lino, Andreia C

Frontiers in immunology

2022 Volume 13, Page(s) 873217

Abstract: Antibody-secreting cells (ASCs) contribute to immunity through production of antibodies and cytokines. Identification of specific markers of ASC would allow selective targeting of these cells in several disease contexts. Here, we performed an unbiased, ... ...

Abstract	Antibody-secreting cells (ASCs) contribute to immunity through production of antibodies and cytokines. Identification of specific markers of ASC would allow selective targeting of these cells in several disease contexts. Here, we performed an unbiased, large-scale protein screening, and identified twelve new molecules that are specifically expressed by murine ASCs. Expression of these markers, particularly CD39, CD81, CD130, and CD326, is stable and offers an improved resolution for ASC identification. We accessed their expression in germ-free conditions and in T cell deficient mice, showing that at least in part their expression is controlled by microbial- and T cell-derived signals. Further analysis of lupus mice revealed the presence of a subpopulation of LAG-3
MeSH term(s)	Animals ; Antibodies, Antinuclear ; Antibody-Producing Cells ; Biomarkers/metabolism ; Bone Marrow/metabolism ; Humans ; Immunoglobulin M ; Mice ; Plasma Cells/metabolism
Chemical Substances	Antibodies, Antinuclear ; Biomarkers ; Immunoglobulin M ; anti-dsDNA autoantibody
Language	English
Publishing date	2022-04-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.873217
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