Immunomodulation of Neutrophils and Platelets by Tnf Blockage in Patients With Juvenile Idiopathic Arthritis

Zuzana Parackova, Irena Zentsova, Rudolf Horvath, Hana Malcova, Dita Cebecauerova, Anna Sediva, Adam Klocperk. Clinical Immunology. December 2022. IF: 10.19. doi

RNDr. Zuzana Paračková, Ph.D.

RNDr. Zuzana Paračková, Ph.D., Department of Immunology, Second Faculty of Medicine and Motol University Hospital


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.

Created: 20. 4. 2023 / Modified: 11. 7. 2023 / Mgr. Stanislava Lindenthalová