Department of Paediatrics, Pediatric Rheumatology. CEREMAI Bicêtre Hospital, University of Paris Sud., France
Service de Biothérapies/ UPMC CNRS 7211 INSERM 959. La Pitié Salpétrière University Hospital. Paris, France
Unité de Recherche Clinique Paris Sud. Bicêtre University Hospital. Le Kremlin Bicêtre. France
Department of Internal Medicine. La Pitié Salpétrière University Hospital, Paris, France
Unité 2. UPMC-CNRS U7087. La Pitié Salpétrière University Hospital, Paris, France
Introduction
Behçet’s disease (BD) is an idiopathic multisystem recurrent inflammatory disorder. Physiopathology of BD shows a role of neutrophils and cytotoxic T lymphocytes.
Our aim
Were to assess the role of regulatory T lymphocytes (Tregs) in the pathogenesis of BD in children.
Patients and methods
19 patients with active BD (group A) and 8 patients with inactive BD (group B) were compared with 25 healthy controls (group C). Percentages of blood CD4+CD127-CD25hiFoxP3+ Tregs and other T/B and NK cells subpopulations were nalayzed by flow cytometry. The frequency of IL-17A and IFN-γ producing T cells was analyzed by flow cytometer from PBMC after 4 hours stimulation with PMA-ionomycin. We measured serum cytokines by Luminex and ELISA. We compared the 3 groups by using the Wilcoxon-Rank-signed test. Values were expressed as mean and median.
Results
Patients in the 3 groups (A, B, C respectively) were comparable in term of age and sex distribution (median age: 12.8, 9,9 and 9.7; F/M = 1/1). No differences were observed between the 3 groups concerning the absolute number of lymphocytes, CD4+ T cells and the percentage of total Tregs (median: A: 1.9, B:1.1, C:2.8) . Percentages of naïve Treg/memory Treg and markers of Treg function (GITR, LAP, CD152, DR) were also similar in the 3 groups. However, there was increased CD8+ T cells count in the BD patients groups compared to healthy controls (A: 552±361, p=0.18; B: 627±159, p=0.04, C: 479±209). The NK cell (CD3-CD16+CD56+) were highest in group C compared to group A (p=0.4) or B (p=0.001). IL-17A secreting CD4+ T cells were significantly higher in active BD patients (n=6) compared to controls (n=6) (5.3±2 vs 2.5±1.47, p=0.043). Serum IL-6 level was significantly hisgher in BD populations compared to controls subjects (A: 4,3±1,22 vs C:3±0,7 pg/ml, p=0,016).
Conclusion
There is no deficit of Tregs number in BD patients. The high rate of peripheral IL-17 secreting CD4+ T cells suggests a possible role of Th17 cells in the occurrence of BD attacks. The Tregs functional ability to regulate CD4 and CD8 T cells needs to be studied further.