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Deutscher Rheumatologiekongress 2024

52. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh)
34. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)
38. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

18.09. - 21.09.2024, Düsseldorf

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TLR8-specific stimulation induces pro-inflammatory cytokine production in peripheral monocytes from patients with systemic sclerosis

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  • Kathleen Friedrich - Medizinische Klinik III, Klinik und Poliklinik Endokrinologie, Nephrologie und Rheumatologie, Bereich Rheumatologie, Leipzig
  • Kathrin Rothe - Medizinische Klinik III, Klinik und Poliklinik Endokrinologie, Nephrologie und Rheumatologie, Bereich Rheumatologie, Leipzig
  • Caroline Schmidt - Medizinische Klinik III, Klinik und Poliklinik Endokrinologie, Nephrologie und Rheumatologie, Bereich Rheumatologie, Leipzig
  • Manuela Rossol - Fakultät für Gesundheitswissenschaften, Molekulare Immunologie, Leipzig
  • Ulf Wagner - Medizinische Klinik III, Klinik und Poliklinik Endokrinologie, Nephrologie und Rheumatologie, Bereich Rheumatologie, Leipzig
  • Matthias Pierer - Medizinische Klinik III, Klinik und Poliklinik Endokrinologie, Nephrologie und Rheumatologie, Bereich Rheumatologie, Leipzig

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. Deutscher Rheumatologiekongress 2024, 52. Kongress der Deutschen Gesellschaft für Rheumatologie und Klinische Immmunologie (DGRh), 34. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR), 38. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh). Düsseldorf, 18.-21.09.2024. Düsseldorf: German Medical Science GMS Publishing House; 2024. DocVK.36

doi: 10.3205/24dgrh214, urn:nbn:de:0183-24dgrh2148

Published: September 18, 2024

© 2024 Friedrich et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Introduction: Systemic sclerosis (SSc) is a rare, chronic autoimmune disease. SSc affects the connective tissue and causes hardening and tightening of the skin. Based on clinical and serologic factors, it can be classified into two forms: limited cutaneous (lc SSc) or diffuse cutaneous (dc SSc) systemic sclerosis. Both, lc SSc and dc SSc, are associated with several systemic manifestations and organ involvement. Because SSc is a rare disease, medical treatment options are infrequent and unspecific. Aim of the study was to identify a novel target to reduce inflammatory processes and decrease disease progression in SSc patients.

Methods: Using FACS analysis of CD14/CD16 surface expression, we investigated peripheral blood monocyte subpopulations from SSc patients (n=38) and healthy controls (n=17). Peripheral blood monocytes were isolated using pan monocyte isolation kit and stimulated with the TLR4 agonist LPS or the TLR8 agonist ssRNA40 with or without hydroxychloroquine. ELISA was used to determine IL-6 and IL-10 in the supernatant and serum.

Results: Our results show that SSc patients had significantly higher frequency of intermediate (mean: 10,6% vs. 7,6%) and non-classical monocytes compared to healthy controls (mean: 15,2% vs. 8,6%) Furthermore, IL-6 serum levels were significantly increased in SSc patients compared to controls. Using TLR8 agonist ssRNA40, SSc monocytes produced significantly higher levels of IL-6 and IL-10 compared to control monocytes. More specifically, dc monocytes from SSc patients predominantly produced IL6 and IL-10. Preliminary results show, that pre-stimulation with hydroxychloroquine was able to block high IL-6 and IL-10 amounts induced by TLR8 stimulation.

Conclusion: In SSc, high amounts of IL-6 and IL-10 support tissue disorder. We are the first to show a significant impact of peripheral blood monocytes and TLR8 signaling on the inflammatory background in SSc. Hydroxychloroquine was able to block this inflammatory cytokine production by monocytes and could be a useful supplement in medical treatment of systemic sclerosis.