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Vaccination leads to an aberrant FOXP3 T-cell response in non-remitting juvenile idiopathic arthritis
  1. Arash Ronaghy,
  2. Wilco de Jager,
  3. Evelien Zonneveld-Huijssoon,
  4. Mark R Klein,
  5. Femke van Wijk,
  6. Ger T Rijkers,
  7. Wietse Kuis,
  8. Nico M Wulffraat,
  9. Berent J Prakken
  1. Department of Pediatrics, Center for Cellular and Molecular Intervention, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to B J Prakken, Department of Pediatric Immunology KC.03.063.0, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands; b.prakken{at}umcutrecht.nl

Abstract

Objective To investigate how meningococcal C vaccination in patients with remitting (oligoarticular) or progressive (polyarticular) juvenile idiopathic arthritis (JIA) influences the specific T-cell response to both the vaccine and heat shock protein 60, a regulatory auto-antigen in JIA.

Methods Twenty six oligoarticular, 28 polyarticular JIA patients and 20 healthy adults were studied before and after MenC vaccination in a prospective follow-up study. T-cell proliferation assay, flow cytometry, carboxyfluorescein diacetate succinimidyl ester staining and multiplex immunoassay were performed to quantify and qualify the antigen-specific immune responses.

Results Peripheral blood mononuclear cells (PBMC) from polyarticular JIA exemplified higher antigen-specific CD4 T-cell proliferation, interleukin 2 (IL-2) and tumour necrosis factor alpha (TNFα) production when compared with oligoarticular JIA or healthy individuals after vaccination. Furthermore, in polyarticular JIA antigen-induced CD4+CD25bright or CD4+FOXP3+ T cells did not increase upon vaccination.

Conclusion Polyarticular JIA CD4+FOXP3+ T cells did not respond to vaccination and demonstrated a higher percentage of cells irrespective of vaccination when compared with oligoarticular JIA. These cells are either activated T cells and/or regulatory cells unable to regulate the antigen-specific immune response after vaccination. When compared with oligoarticular JIA, the increased IL-2 and TNFα production underline the immune hyperresponsiveness of polyarticular JIA PBMC to an antigenic trigger. As this may hold a risk for derailment, these findings could provide a cellular basis for the presumed relationship between environmental triggers and disease in human autoimmune diseases.

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Footnotes

  • BJP and NMW contributed equally to this study.

  • Funding AR was funded by the Fifth Framework Program ‘hsp for therapy’ of the European Commission. BJP is also supported by the Dutch Rheumatoid Arthritis Foundation and by a ‘VIDI’ innovation grant from the Dutch Organisation for Scientific Research. Sponsors of this study had neither involvement in the study design, in collection, analysis and interpretation of data, in writing the report, nor in the decision to submit for publication.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the University Medical Center Utrecht.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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