Immunomodulation of neutrophils and platelets by TNF blockage in patients with juvenile idiopathic arthritis
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 245(2022) vom: 15. Dez., Seite 109170 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2022
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| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Juvenile idiopathic arthritis MMP8 Neutrophil Neutrophil-platelet aggregates Platelet S100 TNF inhibitors |
| Zusammenfassung: | Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. Juvenile idiopathic arthritis (JIA) is a multifactorial autoimmune disease mediated by both adaptive and innate immunity. The role of neutrophils in the pathogenesis of autoimmune diseases is well-established; however, in JIA they are still markedly understudied. Here, we explored the neutrophil features and role of platelet-neutrophil aggregates in JIA patients and assessed the effect of TNF inhibitor (TNFi) therapy. We provide evidence of dysbalanced neutrophil subsets in JIA patients, with a shift towards immature and suppressive subpopulations that lack the cell-adhesion molecules. Correspondingly, patient sera contained high amounts of neutrophil- and platelet-related products. Transcriptomic analysis revealed neutrophil degranulation as the most affected process by TNFi therapy, which was mirrored by the decrease in degranulation products in the patient sera. Toll-like receptors -4, -7, and - 8 signaling pathways are particularly hyperresponsive in patients, but are strongly suppressed by TNFi. Overall, our study demonstrates augmented neutrophil and platelet responses in JIA patients |
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| Beschreibung: | Date Completed 25.11.2022 Date Revised 26.12.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109170 |