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Article ; Online: Cross-reactivity of human monoclonal antibodies with canine peripheral blood mononuclear cells.

Ciftci, Oktay / Müller, Laura Mara / Jäggle, Lisa-Marie / Lehmann, Christine / Kneilmann, Christine / Stierstorfer, Birgit / Roy, Urmi / Witsch, Esther Julia

Veterinary immunology and immunopathology

2023 Volume 259, Page(s) 110578

Abstract: In drug development, the dog is often used as a model for non-rodent preclinical safety studies. In particular, immunophenotyping in dogs can be important to characterize the toxicological profile of a test item. A wide range of antibodies specific to ... ...

Abstract	In drug development, the dog is often used as a model for non-rodent preclinical safety studies. In particular, immunophenotyping in dogs can be important to characterize the toxicological profile of a test item. A wide range of antibodies specific to surface antigens is needed, however, commercially available antibodies to dog are scarce. To date, numerous studies have reported the cross-reactivity of human monoclonal antibodies with canine peripheral blood mononuclear cells (PBMC). In this study, we aimed to increase the number of canine-specific antibodies and took a rather novel approach to further determine cross-reactivity of 378 human recombinant antibodies lacking Fc regions to surface antigens on canine PBMC. The screening resulted in 30 human monoclonal antibodies well reactive to canine PBMC. Sequence homology of the targeted human and canine antigens was analyzed with Basic Local Alignment Search Tool. Thirteen human cross-reactive antibodies of interest were analyzed with cells from canine whole blood in combination with lineage markers. Finally, ten antibodies were identified as useful markers for the application in dog. Except for CD27, the remaining nine antibodies are already commercially available human cross-reactive antibodies. This study provides a new source for all ten antibodies described here.
MeSH term(s)	Humans ; Dogs ; Animals ; Antibodies, Monoclonal ; Leukocytes, Mononuclear ; Cross Reactions ; Antigens, Surface ; Immunophenotyping/veterinary ; Flow Cytometry/veterinary
Chemical Substances	Antibodies, Monoclonal ; Antigens, Surface
Language	English
Publishing date	2023-03-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	754160-0
ISSN	1873-2534 ; 0165-2427
ISSN (online)	1873-2534
ISSN	0165-2427
DOI	10.1016/j.vetimm.2023.110578
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Article ; Online: Erratum to: Dendritic cells as therapeutic targets in neuroinflammation.

Luessi, Felix / Zipp, Frauke / Witsch, Esther

Cellular and molecular life sciences : CMLS

2016 Volume 73, Issue 13, Page(s) 2451

Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article ; Published Erratum
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-016-2227-9
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Zs.A 195: Show issues

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Article ; Online: Array genotyping as diagnostic approach in medical genetics.

Witsch-Baumgartner, Martina / Schwaninger, Gunda / Schnaiter, Simon / Kollmann, Franziska / Burkhard, Silja / Gröbner, Rebekka / Mühlegger, Beatrix / Schamschula, Esther / Kirchmeier, Peter / Zschocke, Johannes

Molecular genetics & genomic medicine

2022 Volume 10, Issue 9, Page(s) e2016

Abstract: Genotyping arrays are by far the most widely used genetic tests but are not generally utilized for diagnostic purposes in a medical context. In the present study, we examined the diagnostic value of a standard genotyping array (Illumina Global Screening ... ...

Abstract	Genotyping arrays are by far the most widely used genetic tests but are not generally utilized for diagnostic purposes in a medical context. In the present study, we examined the diagnostic value of a standard genotyping array (Illumina Global Screening Array) for a range of indications. Applications included stand-alone testing for specific variants (32 variants in 10 genes), first-tier array variant screening for monogenic conditions (10 different autosomal recessive metabolic diseases), and diagnostic workup for specific conditions caused by variants in multiple genes (suspected familial breast and ovarian cancer, and hypercholesterolemia). Our analyses showed a high analytical sensitivity and specificity of array-based analyses for validated and non-validated variants, and identified pitfalls that require attention. Ethical-legal assessment highlighted the need for a software solution that allows for individual indication-based consent and the reliable exclusion of non-consented results. Cost/time assessment revealed excellent performance of diagnostic array analyses, depending on indication, proband data, and array design. We have implemented some analyses in our diagnostic portfolio, but array optimization is required for the implementation of other indications.
MeSH term(s)	Genetic Testing ; Genetics, Medical ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Software
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.2016
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Article ; Online: Dendritic cells as therapeutic targets in neuroinflammation.

Luessi, Felix / Zipp, Frauke / Witsch, Esther

Cellular and molecular life sciences : CMLS

2016 Volume 73, Issue 13, Page(s) 2425–2450

Abstract: Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. There is still no cure for the ... ...

Abstract	Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. There is still no cure for the disease, but drug regimens can reduce the frequency of relapses and slightly delay progression. Myeloid cells or antigen-presenting cells (APCs) such as dendritic cells (DC), macrophages, and resident microglia, are key players in both mediating immune responses and inducing immune tolerance. Mounting evidence indicates a contribution of these myeloid cells to the pathogenesis of multiple sclerosis and to the effects of treatment, the understanding of which might provide strategies for more potent novel therapeutic interventions. Here, we review recent insights into the role of APCs, with specific focus on DCs in the modulation of neuroinflammation in MS.
MeSH term(s)	Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/pathology ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Drug Discovery/methods ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Humans ; Immune Tolerance/drug effects ; Microglia/drug effects ; Microglia/immunology ; Microglia/pathology ; Molecular Targeted Therapy/methods ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/immunology ; Multiple Sclerosis/pathology
Language	English
Publishing date	2016-03-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-016-2170-9
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Article ; Online: Phenotype of Antigen Unexperienced T

Franck, Sophia / Paterka, Magdalena / Birkenstock, Jerome / Zipp, Frauke / Siffrin, Volker / Witsch, Esther

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2017 Volume 12, Issue 2, Page(s) 305–313

Abstract: Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the ... ...

Abstract	Multiple sclerosis is a chronic, disseminated inflammation of the central nervous system which is thought to be driven by autoimmune T cells. Genetic association studies in multiple sclerosis and a large number of studies in the animal model of the disease support a role for effector/memory T helper cells. However, the mechanisms underlying relapses, remission and chronic progression in multiple sclerosis or the animal model experimental autoimmune encephalomyelitis, are not clear. In particular, there is only scarce information on the role of central nervous system-invading naive T helper cells in these processes. By applying two-photon laser scanning microscopy we could show in vivo that antigen unexperienced T helper cells migrated into the deep parenchyma of the inflamed central nervous system in experimental autoimmune encephalomyelitis, independent of their antigen specificity. Using flow cytometric analyses of central nervous system-derived lymphocytes we found that only antigen-specific, formerly naive T helper cells became activated during inflammation of the central nervous system encountering their corresponding antigen.
Language	English
Publishing date	2017-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-016-9718-1
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Article: Dendritic cells as therapeutic targets in neuroinflammation

LÃ¼ssi, Felix / Frauke Zipp / Esther Witsch

Cellular and molecular life sciences. 2016 July, v. 73, no. 13

2016

Abstract	Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. There is still no cure for the disease, but drug regimens can reduce the frequency of relapses and slightly delay progression. Myeloid cells or antigen-presenting cells (APCs) such as dendritic cells (DC), macrophages, and resident microglia, are key players in both mediating immune responses and inducing immune tolerance. Mounting evidence indicates a contribution of these myeloid cells to the pathogenesis of multiple sclerosis and to the effects of treatment, the understanding of which might provide strategies for more potent novel therapeutic interventions. Here, we review recent insights into the role of APCs, with specific focus on DCs in the modulation of neuroinflammation in MS.
Keywords	central nervous system ; dendritic cells ; drugs ; immune response ; immunosuppression ; macrophages ; myelin sheath ; neuroglia ; neurons ; pathogenesis ; sclerosis
Language	English
Dates of publication	2016-07
Size	p. 2425-2450.
Publishing place	Springer International Publishing
Document type	Article
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-016-2170-9
Database	NAL-Catalogue (AGRICOLA)

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Article: Allelic and isotypic light chain inclusion in peripheral B cells from anti-DNA antibody transgenic C57BL/6 and BALB/c mice.

Witsch, Esther J / Bettelheim, Eldad

Journal of immunology (Baltimore, Md. : 1950)

2008 Volume 180, Issue 6, Page(s) 3708–3718

Abstract: Most mature B lymphocytes express one BCR L chain, kappa or lambda, but recent work has shown that there are exceptions in that some B lymphocytes express both kappa and lambda and some even bear two different kappa L chains. Using the anti-DNA H chain- ... ...

Abstract	Most mature B lymphocytes express one BCR L chain, kappa or lambda, but recent work has shown that there are exceptions in that some B lymphocytes express both kappa and lambda and some even bear two different kappa L chains. Using the anti-DNA H chain-transgenic mouse, 56R, we find that B cells with pre-existing autoreactivity are especially subject to L chain inclusion. Specifically, we show that isotypic and allelic inclusion enables autoreactive B cells to bypass central tolerance giving rise to B cells that retain dangerous features. One receptor in dual receptor B cells is an editor L chain, i.e., neutralizes or alters self-reactivity of the 56R H chain transgene. We compare the 56R mouse when on the C57/BL/6 background, a strain prone to autoimmunity, with that of 56R when on the BALB/c background, a strain that resists autoimmunity. In the B6.56R mouse, polyreactive B cells with dual L chain move to the follicular B cell compartment. Their localization in the follicular compartment may explain the ease with which B cells in the B6.56R differentiate into autoantibody-producing plasma cells. Likewise, in the BALB/c.56R mouse, dual L chain B cells are found in the follicular B cell compartment. Yet, the lack of autoantibody-producing plasma cells in the BALB/c.56R suggests that postfollicular tolerance checkpoints are intact. The Jkappa usage in dual kappa L chain B cells suggests increased receptor editing activity and is consistent with the expected distribution of Jkappa genes in our computational model for random selection of Jkappa.
MeSH term(s)	Alleles ; Animals ; Antibodies, Antinuclear/genetics ; B-Lymphocyte Subsets/immunology ; B-Lymphocyte Subsets/metabolism ; Gene Rearrangement, B-Lymphocyte, Light Chain ; Immunoglobulin Constant Regions/biosynthesis ; Immunoglobulin Constant Regions/genetics ; Immunoglobulin Isotypes/biosynthesis ; Immunoglobulin Isotypes/genetics ; Immunoglobulin Variable Region/biosynthesis ; Immunoglobulin Variable Region/genetics ; Immunoglobulin kappa-Chains/biosynthesis ; Immunoglobulin kappa-Chains/genetics ; Immunoglobulin lambda-Chains/biosynthesis ; Immunoglobulin lambda-Chains/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; RNA Editing/genetics ; RNA Editing/immunology ; Receptors, Antigen, B-Cell/genetics ; Receptors, Antigen, B-Cell/immunology ; Spleen/cytology ; Spleen/immunology ; Spleen/metabolism
Chemical Substances	Antibodies, Antinuclear ; Immunoglobulin Constant Regions ; Immunoglobulin Isotypes ; Immunoglobulin Variable Region ; Immunoglobulin kappa-Chains ; Immunoglobulin lambda-Chains ; Receptors, Antigen, B-Cell
Language	English
Publishing date	2008-02-23
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.180.6.3708
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Article ; Online: The Role of ERK Signaling in Experimental Autoimmune Encephalomyelitis.

Birkner, Katharina / Wasser, Beatrice / Loos, Julia / Plotnikov, Alexander / Seger, Rony / Zipp, Frauke / Witsch, Esther / Bittner, Stefan

International journal of molecular sciences

2017 Volume 18, Issue 9

Abstract: Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as ... ...

Abstract	Extracellular signal-regulated kinase (ERK) signaling plays a crucial role in regulating immune cell function and has been implicated in autoimmune disorders. To date, all commercially available inhibitors of ERK target upstream components, such as mitogen-activated protein (MAP) kinase/ERK kinase (MEKs), but not ERK itself. Here, we directly inhibit nuclear ERK translocation by a novel pharmacological approach (Glu-Pro-Glu (EPE) peptide), leading to an increase in cytosolic ERK phosphorylation during T helper (Th)17 cell differentiation. This was accompanied by diminished secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine influencing the encephalitogenicity of Th17 cells. Neither the production of the cytokine interleukin (IL)-17 nor the proliferation rate of T cells was affected by the EPE peptide. The in vivo effects of ERK inhibition were challenged in two independent variants of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Overall, ERK inhibition had only a very minor impact on the clinical disease course of EAE. This indicates that while ERK translocation might promote encephalitogenicity in T cells in vitro by facilitating GM-CSF production, this effect is overcome in more complex in vivo animal models of central nervous system (CNS) autoimmunity.
Language	English
Publishing date	2017-09-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms18091990
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Article ; Online: Roles for growth factors in cancer progression.

Witsch, Esther / Sela, Michael / Yarden, Yosef

Physiology (Bethesda, Md.)

2010 Volume 25, Issue 2, Page(s) 85–101

Abstract: Under physiological conditions, cells receive fate-determining signals from their tissue surroundings, primarily in the form of polypeptide growth factors. Integration of these extracellular signals underlies tissue homeostasis. Although departure from ... ...

Abstract	Under physiological conditions, cells receive fate-determining signals from their tissue surroundings, primarily in the form of polypeptide growth factors. Integration of these extracellular signals underlies tissue homeostasis. Although departure from homeostasis and tumor initiation are instigated by oncogenic mutations rather than by growth factors, the latter are the major regulators of all subsequent steps of tumor progression, namely clonal expansion, invasion across tissue barriers, angiogenesis, and colonization of distant niches. Here, we discuss the relevant growth factor families, their roles in tumor biology, as well as the respective downstream signaling pathways. Importantly, cancer-associated activating mutations that impinge on these pathways often relieve, in part, the reliance of tumors on growth factors. On the other hand, growth factors are frequently involved in evolvement of resistance to therapeutic regimens, which extends the roles for polypeptide factors to very late phases of tumor progression and offers opportunities for cancer therapy.
MeSH term(s)	Disease Progression ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Signal Transduction/physiology
Chemical Substances	Intercellular Signaling Peptides and Proteins
Language	English
Publishing date	2010-04-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2158667-6
ISSN	1548-9221 ; 1548-9213
ISSN (online)	1548-9221
ISSN	1548-9213
DOI	10.1152/physiol.00045.2009
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Article ; Online: Increase of Alternatively Activated Antigen Presenting Cells in Active Experimental Autoimmune Encephalomyelitis.

Wasser, Beatrice / Pramanik, Gautam / Hess, Moritz / Klein, Matthias / Luessi, Felix / Dornmair, Klaus / Bopp, Tobias / Zipp, Frauke / Witsch, Esther

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2016 Volume 11, Issue 4, Page(s) 721–732

Abstract: The importance of ... ...

Abstract	The importance of CD11c
MeSH term(s)	Animals ; Antigen-Presenting Cells/metabolism ; CD11c Antigen/biosynthesis ; CD11c Antigen/genetics ; Dendritic Cells/metabolism ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Gene Regulatory Networks/physiology ; Mice ; Mice, Inbred C57BL
Chemical Substances	CD11c Antigen
Language	English
Publishing date	2016-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-016-9696-3
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