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  1. Article: Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis.

    Papadimitriou, Theodoros-Ioannis / van Caam, Arjan / van der Kraan, Peter M / Thurlings, Rogier M

    Biomedicines

    2022  Volume 10, Issue 2

    Abstract: Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are ... ...

    Abstract Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are currently available. Inflammation, vasculopathy, and fibrosis are the key hallmarks of SSc pathology. In this narrative review, we examine the relationship between inflammation and fibrosis and provide an overview of the efficacy of current and novel treatment options in diminishing SSc-related fibrosis based on selected clinical trials. To do this, we first discuss inflammatory pathways of both the innate and acquired immune systems that are associated with SSc pathophysiology. Secondly, we review evidence supporting the use of first-line therapies in SSc patients. In addition, T cell-, B cell-, and cytokine-specific treatments that have been utilized in SSc are explored. Finally, the potential effectiveness of tyrosine kinase inhibitors and other novel therapeutic approaches in reducing fibrosis is highlighted.
    Language English
    Publishing date 2022-01-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines10020316
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Systemic sclerosis-associated pulmonary arterial hypertension is characterized by a distinct peripheral T helper cell profile.

    Papadimitriou, Theodoros-Ioannis / Lemmers, Jacqueline M J / van Caam, Arjan P M / Vos, Jacqueline / Vitters, Elly / Stinessen, Lizan / van Leuven, Sander I / Koenders, Marije / van der Kraan, Peter M / Koenen, Hans J P M / Smeets, Ruben / Nijveldt, Robin / Vonk, Madelon C / Thurlings, R M

    Rheumatology (Oxford, England)

    2024  

    Abstract: Objectives: Systemic sclerosis (SSc) is characterized by multiple clinical manifestations. Vasculopathy is a main disease hallmark and ranges in severity from an exacerbated Raynaud phenomenon to pulmonary arterial hypertension (PAH). The potential ... ...

    Abstract Objectives: Systemic sclerosis (SSc) is characterized by multiple clinical manifestations. Vasculopathy is a main disease hallmark and ranges in severity from an exacerbated Raynaud phenomenon to pulmonary arterial hypertension (PAH). The potential involvement of immune system in SSc associated vascular abnormalities is not clear. Here, we set out to study SSc-related immune parameters and determine whether and which peripheral T cell subsets associate with vascular severity in SSc patients.
    Methods: Peripheral blood and clinical data were collected from 30 SSc patients, 5 patients with idiopathic pulmonary arterial hypertension (IPAH) and 15 age and sex-matched healthy donors (HD). In this cross-sectional cohort SSc patients with PAH (n = 15) were matched for their age, sex and medication with SSc patients with no signs of PAH (n = 15). Lymphocyte subsets were quantified by multi-colour flow cytometry.
    Results: SSc patients exhibited elevated percentages of T peripheral helper cells (Tph), CD4+GZMB+ T cells and decreased levels of Th1 cells compared with HD. Increased presence of both CD4+ and CD8+ exhausted-like (CD28-) T cells, characterized by raised cytokine and cytotoxic signature, was also observed in SSc compared with HD blood. Furthermore, IL-4 expressing CD4+CD8+ T cells were significantly increased in SSc peripheral blood. Interestingly, the presence of PAH in SSc was accompanied by a distinct T helper profile, characterized by raised percentages of Th17 and Tph cells.
    Conclusion: SSc patients with severe vasculopathy (presence of PAH) exhibited a distinct T cell profile, suggesting for a potential role of auto-immune inflammation in SSc vascular complications.
    Language English
    Publishing date 2024-03-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae190
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.B 240: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 497: Show issues

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  3. Article ; Online: CD7 activation regulates cytotoxicity-driven pathology in systemic sclerosis, yielding a target for selective cell depletion.

    Papadimitriou, Theodoros Ioannis / Singh, Prashant / van Caam, Arjan / Walgreen, Birgitte / Gorris, Mark A J / Vitters, Elly L / van Ingen, Iris L / Koenders, Marije I / Smeets, Ruben L / Vonk, Madelon / de Vries, Jolanda M / van der Kraan, Peter M / van Oosterhout, Ypke / Huynen, Martijn A / Koenen, Hans J P M / Thurlings, Rogier M

    Annals of the rheumatic diseases

    2024  Volume 83, Issue 4, Page(s) 488–498

    Abstract: Objectives: Cytotoxic T cells and natural killer (NK) cells are central effector cells in cancer and infections. Their effector response is regulated by activating and inhibitory receptors. The regulation of these cells in systemic autoimmune diseases ... ...

    Abstract Objectives: Cytotoxic T cells and natural killer (NK) cells are central effector cells in cancer and infections. Their effector response is regulated by activating and inhibitory receptors. The regulation of these cells in systemic autoimmune diseases such as systemic sclerosis (SSc) is less defined.
    Methods: We conducted ex vivo analysis of affected skin and blood samples from 4 SSc patient cohorts (a total of 165 SSc vs 80 healthy individuals) using single-cell transcriptomics, flow cytometry and multiplex immunofluorescence staining. We further analysed the effects of costimulatory modulation in functional assays, and in a severely affected SSc patient who was treated on compassionate use with a novel anti-CD3/CD7 immunotoxin treatment.
    Results: Here, we show that SSc-affected skin contains elevated numbers of proliferating T cells, cytotoxic T cells and NK cells. These cells selectively express the costimulatory molecule CD7 in association with cytotoxic, proinflammatory and profibrotic genes, especially in recent-onset and severe disease. We demonstrate that CD7 regulates the cytolytic activity of T cells and NK cells and that selective depletion of CD7
    Conclusion: Together, the findings imply costimulatory molecules as key regulators of cytotoxicity-driven pathology in systemic autoimmune disease, yielding CD7 as a novel target for selective depletion of pathogenic cells.
    MeSH term(s) Humans ; Antigens, CD7/metabolism ; Killer Cells, Natural ; Scleroderma, Systemic ; T-Lymphocytes
    Chemical Substances Antigens, CD7
    Language English
    Publishing date 2024-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 7090-7
    ISSN 1468-2060 ; 0003-4967
    ISSN (online) 1468-2060
    ISSN 0003-4967
    DOI 10.1136/ard-2023-224827
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.114: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 167: Show issues

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