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THU0294 Regulatory T cells/TH17 balance in the pathogenesis of pediatric behçet disease
  1. T.-A. Tran1,
  2. A. Hubert2,
  3. A. Letierce3,
  4. B. Terrier2,
  5. G. Geri2,
  6. D. Saadoun4,
  7. I. Kone-Paut5,
  8. M. Rosenzwajg2
  1. 1Pediatrics, Pediatric Rheumatology, Cérémai, Inserm U1012, Bicêtre Hospital, University of Paris Sud, Le Kremlin Bicêtre
  2. 2Service de Biothérapies, UPMC CNRS 7211 INSERM 959. La Pitié Salpêtrière university hospital, Paris
  3. 3Unité de Recherche Clinique Paris Sud, Bicêtre university hospital, Le Kremlin Bicêtre
  4. 4Department of Internal Medicine, La Pitié Salpêtrière Hospital, Paris
  5. 5Pediatrics, Pediatric Rheumatology, Cérémai, Bicêtre Hospital, University of Paris Sud, Le Kremlin Bicêtre, France

Abstract

Background Behçet disease (BD) is an idiopathic systemic inflammatory disorder of unknown origin characterizedby recurrent attacks involving the muco-cutaneous, ocular, intestinal, vascular and nervous systems. In adult, it has been shown that Th17 and CD4+FoxP3 regulatory T cells (Tregs) were involved in the pathogenesis of the disease. The promotion of Th17 responses and the suppression of Tregs were induced by IL-21 production (1).

Objectives To determine the nature of T cells driving inflammatory lesions in BD and more precisely the role of regulatory T lymphocytes (Tregs)/Th17 balance in the pathogenesis of BD in children.

Methods Patients with active BD (n=24) and BD patients in remission (n=12) were compared to aged matched healthy subjects (n=25). Percentage and phenotype of Treg (CD4+CD25hiCD127-/loFoxp3+) as well as Th1,Th17/Treg functions after polyclonal (OKT3/IL-2) or antigen specific stimulation (Streptococcus sanguis KTH-1 peptides: BES-1229-243, BES-1373-385, Brn-3b or HSP-60) were assessed by flow cytometry. Serum cytokines were measured by Luminex technology. We compared the 3 groups of subjects by using the Wilcoxon-Rank-signed test. Values were expressed as mean and median.

Results In active and inactive BD patients, Treg levels and other functional Treg markers (GITR, LAP, CD152, HLA-DR) were similar to healthy control in peripheral blood. However, IL-6 was increased in serum and the percentage of IL-17 production CD4+ T cells after polyclonal activation was significantly higher in active BD patients compared to controls (5.3±2 vs 2.5±1.47, p=0.043). There was no significant difference in the percentage of IL-21 production CD4+ T cells between the different groups of subjects. Th1 (IFN-γ secreting cells) CD4+ responses analysis to streptococcal antigens, potentially responsible in BD flare, were similar in BD patients and control subjects. However, Th17 (IL-17 secreting cells) CD4+ responses to specific stimulations were significantly higher in active BD patients compared to controls. When Tregs were removed from total T cells, specific T cell responses were markedly increased in BD patients compared to controls.

Conclusions Tregs number is normal in Pediatric BD patients and the disease is characterized by a Th17 polarization. By contrast to adult BD, IL-21 is not inscreased in BD children. BD flare in children seems to be associated with specific streptococcal antigens T cell response, which is characterized by strong Th17 responses. Despite, the presence of functionally active Tregs, the effector response is not sufficiently counter-balanced to prevent BD flare attacks.

  1. Geri G, Terrier B, Rosenzwajg M, Wechsler B, Touzot M, Seilhean D, Tran TA, Bodaghi B, Musset L, Klatzmann D, Cacoub P, Saadoun D. Critical role of IL-21 in modulating Th17 and regulatory T cells in Behçet’s disease. J Aller Clin Immunol 2011 Sep;128(3):655-64.

Disclosure of Interest None Declared

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