gms | German Medical Science

47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

04.09. - 07.09.2019, Dresden

IL-21-expressing effector T cells drive B-cell dysregulation in the joints of patients with Antinuclear Antibody positive Juvenile Idiopathic Arthritis

Meeting Abstract

  • Jonas Fischer - University Hospital Würzburg, Pediatric Rheumatology, Würzburg
  • Johannes Dirks - University Hospital Würzburg, Pediatric Rheumatology, Würzburg
  • Annette Holl-Wieden - Universitäts-Kinderklinik Würzburg, Kinderrheumatologie, Würzburg
  • Stephan Hackenberg - University Hospital Würzburg, Department of Otorhinolaryngology, Head and Neck Surgery, Würzburg
  • Hermann Girschick - Vivantes Klinikum im Friedrichshain, Klinik für Kinder- und Jugendmedizin, Berlin
  • Henner Morbach - Universitäts-Kinderklinik, Würzburg

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Dresden, 04.-07.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocKR.33

doi: 10.3205/19dgrh192, urn:nbn:de:0183-19dgrh1922

Published: October 8, 2019

© 2019 Fischer 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

Text

Background: Antinuclear antibody (ANA) positivity encompass a clinically homogenous group of patients with juvenile idiopathic arthritis (JIA) characterized by early diseases onset, high risk of uveitis and female preponderance. However, less is known whether ANA+ JIA patients also share a common disease pathogenesis. Our aim was to analyze the cytokine pattern and phenotype of CD4+ T cells in the synovial fluid of ANA+ JIA patients.

Methods: Mononuclear cells were separated from peripheral blood and synovial fluid of 32 JIA patients. The phenotype and cytokine profile of synovial fluid CD4+ cells was analyzed by flow cytometry and compared between JIA subgroups and to TFH cells derived from tonsils. The functional impact of T-cell subsets on B cell activation was assessed in in vitro assay using sorted T cells and B cells.

Results: ANA+ JIA patients showed increased frequencies of IL-21 expressing synovial fluid CD4+ T cells compared to ANA- patients. These IL-21+ CD4+ T-cells co-expressed IFN-y and TNF-a but not IL-17. IL-21 expression of CD4+ synovial fluid T-cells was confined to a PD-1hi T-cell subset which could mimic follicular helper cells (TFH). However, unlike tonsillar TFH cells, synovial fluid PD-1hi T-cells did not express CXCR5 or BCL-6 and rather displayed a phenotype of effector memory T-cells. Both, tonsillar TFH cells and synovial fluid PD-1hi T-cells induced plasma cell differentiation in vitro, however, unlike classical TFH cells the synovial fluid PD-1hi T-cells additionally shifted B-cells towards a CD21lo/-CD11c+T-bet+ B-cell phenotype in vitro. Additionally, CD21lo/-T-bet+ atypical memory B-cells were enriched in the joints of ANA+ JIA patients and their frequency significantly correlated with the presence of IL-21 expressing CD4+ T-cells.

Conclusion: A distinct population of poly-functional “Th-1/21” effector T-cell cells are expanded in the synovial fluid of ANA+ JIA patients. The correlation between this T-cell subset and CD21lo/- T-bet+ atypical memory B-cells and the presence of ANAs suggests a role of these T-cells in the uncontrolled activation of autoreactive B cells. Additionally, IL-21 expression in activated CD4+ effector T-cells seems to be a characteristic signature in the joints of ANA+ JIA patients.