Artikel
IgG derived from systemic sclerosis and giant cell arteritis patients evokes a different cytokine response of THP-1 cells than healthy control IgG
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Autoren
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Paulina Mackedanz
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
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Hanna Graßhoff
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
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Alexander Maximilian Hackel
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
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Sripriya Murthy
- Department of Dermatology, University of Lübeck, Lübeck
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Hauke Busch
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck
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Christian Sadik
- Department of Dermatology, University of Lübeck, Lübeck
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Antje Müller
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
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Anja Schumann
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
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Axel Künstner
- Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck
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Gabriela Riemekasten
- Department of Rheumatology & Clinical Immunology, University of Lübeck, Lübeck
| Veröffentlicht: | 31. August 2022 |
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Gliederung
Text
Introduction: Systemic sclerosis (SSc) is a connective tissue disease displaying characteristic symptoms such as dysfunction of the immune system, microvascular damage and fibrosis. The circulating cytokine profile of SSc patients differs from the one of healthy controls (HC) [1]. For instance, CCL24 is increased in SSc patients [2]. The aim of our study was to determine whether IgG derived from SSc and giant cell arteritis (GCA) patients leads to different cytokine secretion of THP-1 cells compared to IgG from HC.
Methods: THP-1 cells were stimulated with affinity-purified IgG (1 mg/mL, 24 hours) derived from serum of SSc patients (n=7), GCA patients (n=4) and HC (n=10) as well as IVIG. The data were evaluated together with results from a previous experiment [3]. All patients were clinically characterized as well as age- and sex-matched, apart from GCA where, due to disease onset, age matching to HC or SSc was impossible. Levels of secreted cytokines were measured using the RayBio Human Cytokine Antibody Array G-Series 5. For statistical analysis, principal component analysis and linear regression were applied.
Results: The principal component analysis showed no clustering of SSc, GCA or HC. However, the linear regression analysis yielded that treatment with SSc-IgG and GCA-IgG led to a higher secretion of MIF (macrophage migration inhibitory factor) than HC-IgG. After treatment with both, SSc-IgG and GCA-IgG, the secretion of numerous cytokines or related molecules (n=21) was altered in comparison to IVIG. For example, eight chemokines and two interleukins belonging to pro-inflammatory cytokines or cytokines which are chemotactic for immune cells displayed elevated amounts following SSc-IgG and GCA-IgG. Following treatment with SSc-IgG, secretion of IGFBP1 (insulin like growth factor binding protein 1), NTF4 (Neurotrophin 4) and FGF7 (Fibroblast growth factor 7) was higher, while CCL26, EGF (epidermal growth factor) and CSF1 (colony stimulating factor 1) had lower values compared to IVIG.
Conclusion: In vitro treatment of monocytic cell lines such as THP-1 with IgG derived from patients with chronic inflammatory and autoimmune diseases yields distinct patterns of cytokine secretion. To use such cytokine patterns for discrimination between diseases or manifestations, experimental conditions need to be optimized.
Disclosures: Nothing to declare.
References
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- Murthy S, Wannick M, Eleftheriadis G, Müller A, Luo J, Busch H, Dalmann A, Riemekasten G, Sadik CD. Immunoglobin G of systemic sclerosis patients programs a proinflammatory and profibrotic phenotype in monocyte-like THP-1 cells. Rheumatology (Oxford). 2020 Nov 23.
