The Experts below are selected from a list of 453 Experts worldwide ranked by ideXlab platform

Cornelia A. Deeg - One of the best experts on this subject based on the ideXlab platform.

  • Immunological Insights in Equine Recurrent Uveitis.
    Frontiers in immunology, 2021
    Co-Authors: Roxane L. Degroote, Cornelia A. Deeg
    Abstract:

    Horses worldwide suffer from Equine Recurrent Uveitis (ERU), an organ-specific, immune-mediated disease with painful, remitting-relapsing inflammatory attacks alternating with periods of quiescence, which ultimately leads to blindness. In course of disease, both eyes can eventually be affected and since blind horses pose a threat to themselves and their surroundings, these animals have to be killed. Therefore, this disease is highly relevant for veterinary medicine. Additionally, ERU shows strong clinical and pathological resemblance to autoimmune Uveitis in man. The exact cause for the onset of ERU is unclear to date. T cells are believed to be the main effector cells in this disease, as they overcome the blood retinal barrier to invade the eye, an organ physiologically devoid of peripheral immune cells. These cells cause severe intraocular inflammation, especially in their primary target, the retina. With every inflammatory episode, retinal degeneration increases until eyesight is completely lost. In ERU, T cells show an activated phenotype, with enhanced deformability and migration ability, which is reflected in the composition of their proteome and downstream interaction pathways even in quiescent stage of disease. Besides the dysregulation of adaptive immune cells, emerging evidence suggests that cells of the innate immune system may also directly contribute to ERU pathogenesis. As investigations in both the target organ and the periphery have rapidly evolved in recent years, giving new insights on pathogenesis-associated processes on cellular and molecular level, this review summarizes latest developments in ERU research.

  • Deviant proteome profile of Equine granulocytes associates to latent activation status in organ specific autoimmune disease.
    Journal of proteomics, 2020
    Co-Authors: Maria Weigand, Cornelia A. Deeg, Stefanie M. Hauck, Roxane L. Degroote
    Abstract:

    Abstract Equine Recurrent Uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from Equine Recurrent Uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p  1.2), representing 4.1% of total granulocyte proteome. Within these differential identifications, calgranulin B, a protein associated with pathogenesis in other autoimmune diseases, showed highest abundance in Equine Recurrent Uveitis (18 fold). For a better interpretation of the results from our hypothesis-generating approach, we added a threshold for biological significance (ratio ERU/controls >2: 36 proteins) to the proteins with increased abundance in Equine Recurrent Uveitis and analyzed their allocation to the subsets within the Immune System superpathway. The 36 differentially abundant proteins predominantly associated to RAF/MAP kinase cascade, MHC-I-mediated antigen presentation and neutrophil degranulation, suggesting a latently activated phenotype of these innate immune cells in disease. Raw data are available via ProteomeXchange with identifier PXD013648 . Significance Our study provides new insights into the protein repertoire of primary Equine granulocytes and identifies protein abundance changes associated to Equine Recurrent Uveitis (ERU), an organ specific, spontaneously occurring autoimmune disease. We show that granulocyte proteins with increased abundance in ERU strongly associate to RAF/MAP kinase signaling, MHC-I antigen presentation and neutrophil degranulation, pointing to a more activated state of these cells in ERU cases. Since cells were obtained in quiescent stage of disease, latent activation of granulocytes underlines the role of these innate immune cells in ERU. These findings are highly relevant for veterinary medicine, further establishing the importance of granulocytes in this T cell-driven autoimmune disease. Moreover, they have translational quality for autoimmune Uveitis in man, due to strong similarity in disease occurrence, progression and pathogenesis.

  • Neutrophil Extracellular Traps in the Pathogenesis of Equine Recurrent Uveitis (ERU)
    Cells, 2019
    Co-Authors: Leonie Fingerhut, Cornelia A. Deeg, Bernhard Ohnesorge, Myriam Von Borstel, Ariane Schumski, Katrin Strutzberg-minder, Matthias Mörgelin, Henk P. Haagsman, Andreas Beineke, Maren Von Köckritz-blickwede
    Abstract:

    Equine Recurrent Uveitis (ERU) is considered one of the most important eye diseases in horses and typically appears with relapsing inflammatory episodes without systemic effects. Various disorders have been described as an initial trigger, including infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. We investigated whether neutrophil extracellular traps (NETs) are part of the ERU pathogenesis. Therefore, vitreous body fluids (VBF), sera, and histological sections of the eye from ERU-diseased horses were analyzed for the presence of NET markers and compared with horses with healthy eyes. In addition, NET formation by blood derived neutrophils was investigated in the presence of VBF derived from horses with healthy eyes versus ERU-diseased horses using immunofluorescence microscopy. Interestingly, NET markers like free DNA, histone-complexes, and myeloperoxidase were detected in higher amounts in samples from ERU-diseased horses. Furthermore, in vitro NET formation was higher in neutrophils incubated with VBF from diseased horses compared with those animals with healthy eyes. Finally, we characterized the ability of Equine cathelicidins to induce NETs, as potential NET inducing factors in ERU-diseased horses. In summary, our findings lead to the hypothesis that ERU-diseased horses develop more NETs and that these may contribute to the pathogenesis of ERU.

  • Retinal glycoprotein enrichment by concanavalin a enabled identication of novel membrane autoantigen synaptotagmin-1 in Equine Recurrent Uveitis, PLoS One
    2016
    Co-Authors: Margarete E. Swadzba, Barbara Amann, Stefanie M. Hauck, Hassan Y. Naim, Cornelia A. Deeg
    Abstract:

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like Equine Recurrent Uveitis (ERU), a spontaneous model for human autoimmune Uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role i

  • Article Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
    2016
    Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. Deeg
    Abstract:

    Abstract: Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, Equine Recurrent Uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectabl

Stefanie M. Hauck - One of the best experts on this subject based on the ideXlab platform.

  • Deviant proteome profile of Equine granulocytes associates to latent activation status in organ specific autoimmune disease.
    Journal of proteomics, 2020
    Co-Authors: Maria Weigand, Cornelia A. Deeg, Stefanie M. Hauck, Roxane L. Degroote
    Abstract:

    Abstract Equine Recurrent Uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from Equine Recurrent Uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p  1.2), representing 4.1% of total granulocyte proteome. Within these differential identifications, calgranulin B, a protein associated with pathogenesis in other autoimmune diseases, showed highest abundance in Equine Recurrent Uveitis (18 fold). For a better interpretation of the results from our hypothesis-generating approach, we added a threshold for biological significance (ratio ERU/controls >2: 36 proteins) to the proteins with increased abundance in Equine Recurrent Uveitis and analyzed their allocation to the subsets within the Immune System superpathway. The 36 differentially abundant proteins predominantly associated to RAF/MAP kinase cascade, MHC-I-mediated antigen presentation and neutrophil degranulation, suggesting a latently activated phenotype of these innate immune cells in disease. Raw data are available via ProteomeXchange with identifier PXD013648 . Significance Our study provides new insights into the protein repertoire of primary Equine granulocytes and identifies protein abundance changes associated to Equine Recurrent Uveitis (ERU), an organ specific, spontaneously occurring autoimmune disease. We show that granulocyte proteins with increased abundance in ERU strongly associate to RAF/MAP kinase signaling, MHC-I antigen presentation and neutrophil degranulation, pointing to a more activated state of these cells in ERU cases. Since cells were obtained in quiescent stage of disease, latent activation of granulocytes underlines the role of these innate immune cells in ERU. These findings are highly relevant for veterinary medicine, further establishing the importance of granulocytes in this T cell-driven autoimmune disease. Moreover, they have translational quality for autoimmune Uveitis in man, due to strong similarity in disease occurrence, progression and pathogenesis.

  • Retinal glycoprotein enrichment by concanavalin a enabled identication of novel membrane autoantigen synaptotagmin-1 in Equine Recurrent Uveitis, PLoS One
    2016
    Co-Authors: Margarete E. Swadzba, Barbara Amann, Stefanie M. Hauck, Hassan Y. Naim, Cornelia A. Deeg
    Abstract:

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like Equine Recurrent Uveitis (ERU), a spontaneous model for human autoimmune Uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role i

  • Article Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
    2016
    Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. Deeg
    Abstract:

    Abstract: Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, Equine Recurrent Uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectabl

  • Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
    International journal of molecular sciences, 2015
    Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. Deeg
    Abstract:

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, Equine Recurrent Uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in Uveitis.

  • The Equine CD4
    Dataset Papers in Science, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Marius Ueffing, Sandra Helm, Ute Klein, Ramona Schmitt, Cornelia A. Deeg
    Abstract:

    CD4+ T cells are key players in immunology and disease pathology, including relapsing autoimmune Uveitis. Equine Recurrent Uveitis is the only spontaneous animal model for this disease in man. Knowledge about the CD4+ cell proteome is crucial for studies on possible changes in proteome expression of CD4+ effector cells in disease. For this purpose, we generated a reference dataset of the Equine CD4+ cell proteome by sorting Equine CD4+ lymphocytes followed by analysis of whole cell lysate as well as membrane protein fraction using mass spectrometry.

Barbara Amann - One of the best experts on this subject based on the ideXlab platform.

  • Retinal glycoprotein enrichment by concanavalin a enabled identication of novel membrane autoantigen synaptotagmin-1 in Equine Recurrent Uveitis, PLoS One
    2016
    Co-Authors: Margarete E. Swadzba, Barbara Amann, Stefanie M. Hauck, Hassan Y. Naim, Cornelia A. Deeg
    Abstract:

    Complete knowledge of autoantigen spectra is crucial for understanding pathomechanisms of autoimmune diseases like Equine Recurrent Uveitis (ERU), a spontaneous model for human autoimmune Uveitis. While several ERU autoantigens were identified previously, no membrane protein was found so far. As there is a great overlap between glycoproteins and membrane proteins, the aim of this study was to test whether pre-enrichment of retinal glycoproteins by ConA affinity is an effective tool to detect autoantigen candidates among membrane proteins. In 1D Western blots, the glycoprotein preparation allowed detection of IgG reactions to low abundant proteins in sera of ERU patients. Synaptotagmin-1, a Ca2+-sensing protein in synaptic vesicles, was identified as autoantigen candidate from the pre-enriched glycoprotein fraction by mass spectrometry and was validated as a highly prevalent autoantigen by enzyme-linked immunosorbent assay. Analysis of Syt1 expression in retinas of ERU cases showed a downregulation in the majority of ERU affected retinas to 24%. Results pointed to a dysregulation of retinal neurotransmitter release in ERU. Identification of synaptotagmin-1, the first cell membrane associated autoantigen in this spontaneous autoimmune disease, demonstrated that examination of tissue fractions can lead to the discovery of previously undetected novel autoantigens. Further experiments will address its role i

  • Article Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
    2016
    Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. Deeg
    Abstract:

    Abstract: Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, Equine Recurrent Uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectabl

  • Novel Localization of Peripherin 2, the Photoreceptor-Specific Retinal Degeneration Slow Protein, in Retinal Pigment Epithelium
    International journal of molecular sciences, 2015
    Co-Authors: Patrizia B. Uhl, Barbara Amann, Stefanie M. Hauck, Cornelia A. Deeg
    Abstract:

    Retinal pigment epithelium (RPE) builds the outer blood-retinal barrier of the eye. Since one typical feature of the autoimmune disease, Equine Recurrent Uveitis (ERU), is the breakdown of this barrier, we recently performed comparative analysis of healthy and uveitic RPE. We identified for the first time peripherin 2, which is responsible for visual perception and retina development, to be localized in RPE. The purpose of this study was therefore to validate our findings by characterizing the expression patterns of peripherin 2 in RPE and retina. We also investigated whether peripherin 2 expression changes in ERU and if it is expressed by the RPE itself. Via immunohistochemistry, significant downregulation of peripherin 2 in uveitic RPE compared to the control was detectable, but there was no difference in healthy and uveitic retina. A further interesting finding was the clear distinction between peripherin 2 and the phagocytosis marker, rhodopsin, in healthy RPE. In conclusion, changes in the expression pattern of peripherin 2 selectively affect RPE, but not retina, in ERU. Moreover, peripherin 2 is clearly detectable in healthy RPE due to both phagocytosis and the expression by the RPE cells themselves. Our novel findings are very promising for better understanding the molecular mechanisms taking place on RPE in Uveitis.

  • Unraveling the Equine Lymphocyte Proteome: Differential Septin 7 Expression Associates with Immune Cells in Equine Recurrent Uveitis
    PloS one, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Barbara Amann, Marius Ueffing, Sieglinde Hirmer, Cornelia A. Deeg
    Abstract:

    Equine Recurrent Uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in Equine Recurrent Uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the Equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate - polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in Equine Recurrent Uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  • Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune Uveitis.
    Journal of proteome research, 2013
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Barbara Amann, Marius Ueffing, Manfred Stangassinger, Gudrun Treutlein, Kristina J. H. Fröhlich, Elisabeth Kremmer, Juliane Merl, Cornelia A. Deeg
    Abstract:

    Autoimmune Uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine Recurrent Uveitis (ERU) is a valuable spontaneous model for autoimmune Uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease.

Marius Ueffing - One of the best experts on this subject based on the ideXlab platform.

  • The Equine CD4
    Dataset Papers in Science, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Marius Ueffing, Sandra Helm, Ute Klein, Ramona Schmitt, Cornelia A. Deeg
    Abstract:

    CD4+ T cells are key players in immunology and disease pathology, including relapsing autoimmune Uveitis. Equine Recurrent Uveitis is the only spontaneous animal model for this disease in man. Knowledge about the CD4+ cell proteome is crucial for studies on possible changes in proteome expression of CD4+ effector cells in disease. For this purpose, we generated a reference dataset of the Equine CD4+ cell proteome by sorting Equine CD4+ lymphocytes followed by analysis of whole cell lysate as well as membrane protein fraction using mass spectrometry.

  • Unraveling the Equine Lymphocyte Proteome: Differential Septin 7 Expression Associates with Immune Cells in Equine Recurrent Uveitis
    PloS one, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Barbara Amann, Marius Ueffing, Sieglinde Hirmer, Cornelia A. Deeg
    Abstract:

    Equine Recurrent Uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in Equine Recurrent Uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the Equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate - polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in Equine Recurrent Uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  • The Equine CD4+ Lymphocyte Proteome
    Hindawi Publishing Corporation, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Marius Ueffing, Sandra Helm, Ute Klein, Ramona Schmitt, Cornelia A. Deeg
    Abstract:

    CD4+ T cells are key players in immunology and disease pathology, including relapsing autoimmune Uveitis. Equine Recurrent Uveitis is the only spontaneous animal model for this disease in man. Knowledge about the CD4+ cell proteome is crucial for studies on possible changes in proteome expression of CD4+ effector cells in disease. For this purpose, we generated a reference dataset of the Equine CD4+ cell proteome by sorting Equine CD4+ lymphocytes followed by analysis of whole cell lysate as well as membrane protein fraction using mass spectrometry

  • Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune Uveitis.
    Journal of proteome research, 2013
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Barbara Amann, Marius Ueffing, Manfred Stangassinger, Gudrun Treutlein, Kristina J. H. Fröhlich, Elisabeth Kremmer, Juliane Merl, Cornelia A. Deeg
    Abstract:

    Autoimmune Uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine Recurrent Uveitis (ERU) is a valuable spontaneous model for autoimmune Uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease.

  • Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2007, Article ID 39245, 6 pages doi:10.1155/2007/39245 Research Article CRALBP is a Highly Prevalent Autoantigen for
    2013
    Co-Authors: Human Autoimmune Uveitis, Albert J Raith, Cornelia A. Deeg, Stefanie M. Hauck, Barbara Amann, Gerhild Wildner, Stephan R. Thurau, John W. Crabb, Marius Ueffing, Manfred Stangassinger
    Abstract:

    Cellular retinaldehyde binding protein (CRALBP) is an autoantigen in spontaneous Equine Recurrent Uveitis. In order to test whether CRALBP contributes to human autoimmune Uveitis, the specificity of antibodies from human Uveitis patient’s sera was first evaluated in two-dimensional (2D) Western blot analysis. Subsequent identification of the immunoreactive proteins by mass spectrometry resulted in the identification of CRALBP as a putative autoantigen. Additionally, sera from human Uveitis and control patients were by Western blot using purified human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently (P <.01) in human Uveitis patients than in normal controls. Thirty out of 56 tested Uveitis patient’s sera contained autoantibodies reactive against CRALBP, compared to only four out of 23 normal control subjects. The presence of CRALBP autoantibodies in 54 % of tested Uveitis patients supports CRALBP as a possible autoantigen in human autoimmune Uveitis. Copyright © 2007 Cornelia A. Deeg et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Roxane L. Degroote - One of the best experts on this subject based on the ideXlab platform.

  • Immunological Insights in Equine Recurrent Uveitis.
    Frontiers in immunology, 2021
    Co-Authors: Roxane L. Degroote, Cornelia A. Deeg
    Abstract:

    Horses worldwide suffer from Equine Recurrent Uveitis (ERU), an organ-specific, immune-mediated disease with painful, remitting-relapsing inflammatory attacks alternating with periods of quiescence, which ultimately leads to blindness. In course of disease, both eyes can eventually be affected and since blind horses pose a threat to themselves and their surroundings, these animals have to be killed. Therefore, this disease is highly relevant for veterinary medicine. Additionally, ERU shows strong clinical and pathological resemblance to autoimmune Uveitis in man. The exact cause for the onset of ERU is unclear to date. T cells are believed to be the main effector cells in this disease, as they overcome the blood retinal barrier to invade the eye, an organ physiologically devoid of peripheral immune cells. These cells cause severe intraocular inflammation, especially in their primary target, the retina. With every inflammatory episode, retinal degeneration increases until eyesight is completely lost. In ERU, T cells show an activated phenotype, with enhanced deformability and migration ability, which is reflected in the composition of their proteome and downstream interaction pathways even in quiescent stage of disease. Besides the dysregulation of adaptive immune cells, emerging evidence suggests that cells of the innate immune system may also directly contribute to ERU pathogenesis. As investigations in both the target organ and the periphery have rapidly evolved in recent years, giving new insights on pathogenesis-associated processes on cellular and molecular level, this review summarizes latest developments in ERU research.

  • Deviant proteome profile of Equine granulocytes associates to latent activation status in organ specific autoimmune disease.
    Journal of proteomics, 2020
    Co-Authors: Maria Weigand, Cornelia A. Deeg, Stefanie M. Hauck, Roxane L. Degroote
    Abstract:

    Abstract Equine Recurrent Uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from Equine Recurrent Uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p  1.2), representing 4.1% of total granulocyte proteome. Within these differential identifications, calgranulin B, a protein associated with pathogenesis in other autoimmune diseases, showed highest abundance in Equine Recurrent Uveitis (18 fold). For a better interpretation of the results from our hypothesis-generating approach, we added a threshold for biological significance (ratio ERU/controls >2: 36 proteins) to the proteins with increased abundance in Equine Recurrent Uveitis and analyzed their allocation to the subsets within the Immune System superpathway. The 36 differentially abundant proteins predominantly associated to RAF/MAP kinase cascade, MHC-I-mediated antigen presentation and neutrophil degranulation, suggesting a latently activated phenotype of these innate immune cells in disease. Raw data are available via ProteomeXchange with identifier PXD013648 . Significance Our study provides new insights into the protein repertoire of primary Equine granulocytes and identifies protein abundance changes associated to Equine Recurrent Uveitis (ERU), an organ specific, spontaneously occurring autoimmune disease. We show that granulocyte proteins with increased abundance in ERU strongly associate to RAF/MAP kinase signaling, MHC-I antigen presentation and neutrophil degranulation, pointing to a more activated state of these cells in ERU cases. Since cells were obtained in quiescent stage of disease, latent activation of granulocytes underlines the role of these innate immune cells in ERU. These findings are highly relevant for veterinary medicine, further establishing the importance of granulocytes in this T cell-driven autoimmune disease. Moreover, they have translational quality for autoimmune Uveitis in man, due to strong similarity in disease occurrence, progression and pathogenesis.

  • The Equine CD4
    Dataset Papers in Science, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Marius Ueffing, Sandra Helm, Ute Klein, Ramona Schmitt, Cornelia A. Deeg
    Abstract:

    CD4+ T cells are key players in immunology and disease pathology, including relapsing autoimmune Uveitis. Equine Recurrent Uveitis is the only spontaneous animal model for this disease in man. Knowledge about the CD4+ cell proteome is crucial for studies on possible changes in proteome expression of CD4+ effector cells in disease. For this purpose, we generated a reference dataset of the Equine CD4+ cell proteome by sorting Equine CD4+ lymphocytes followed by analysis of whole cell lysate as well as membrane protein fraction using mass spectrometry.

  • Unraveling the Equine Lymphocyte Proteome: Differential Septin 7 Expression Associates with Immune Cells in Equine Recurrent Uveitis
    PloS one, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Barbara Amann, Marius Ueffing, Sieglinde Hirmer, Cornelia A. Deeg
    Abstract:

    Equine Recurrent Uveitis is a spontaneous, lymphocyte-driven autoimmune disease. It affects horses worldwide and presents with painful remitting-relapsing inflammatory attacks of inner eye structures eventually leading to blindness. Since lymphocytes are the key players in Equine Recurrent Uveitis, we were interested in potential changes of their protein repertoire which may be involved in disease pathogenesis. To create a reference for differential proteome analysis, we first unraveled the Equine lymphocyte proteome by two-dimensional sodium dodecyl sulfate - polyacrylamide gel electrophoresis and subsequently identified 352 protein spots. Next, we compared lymphocytes from ERU cases and healthy horses with a two-dimensional fluorescence difference in gel electrophoresis approach. With this technique, we identified seven differentially expressed proteins between conditions. One of the significantly lower expressed candidates, septin 7, plays a role in regulation of cell shape, motility and migration. Further analyses revealed T cells as the main cell type with decreased septin 7 abundance in Equine Recurrent Uveitis. These findings point to a possible pathogenetic role of septin 7 in this sight-threatening disease.

  • The Equine CD4+ Lymphocyte Proteome
    Hindawi Publishing Corporation, 2014
    Co-Authors: Roxane L. Degroote, Stefanie M. Hauck, Marius Ueffing, Sandra Helm, Ute Klein, Ramona Schmitt, Cornelia A. Deeg
    Abstract:

    CD4+ T cells are key players in immunology and disease pathology, including relapsing autoimmune Uveitis. Equine Recurrent Uveitis is the only spontaneous animal model for this disease in man. Knowledge about the CD4+ cell proteome is crucial for studies on possible changes in proteome expression of CD4+ effector cells in disease. For this purpose, we generated a reference dataset of the Equine CD4+ cell proteome by sorting Equine CD4+ lymphocytes followed by analysis of whole cell lysate as well as membrane protein fraction using mass spectrometry