Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
AntiTnf Therapy, but Not Methotrexate (MTX), Affects the Balance Between CD4CD25FOXP3 Regulatory T Cells (Tregs) and Th17 Cells in Children with Juvenile Idiopathic Arthritis (JIA)
Olivito, Biagio, Simonini, Gabriele, Rossi, Gabriele, Betti, Letizia, Moriondo, Maria, de Martino, Maurizio, Azzari, Chiara
AntiTNFa therapy has become a valid and important treatment option for children with JIA although its role in modulating Tregs and Th17 cells has not fully elucidated, particularly in this disease. We therefore investigated the percentage and surface phenotype of Tregs and Th17 cells from JIA children before and after treatment with two anti-TNFa inhibitors currently available (Adalimumab and Etanercept), comparing them with both healthy children and patients treated with MTX.
Peripheral blood mononuclear cells (PBMCs) were obtained from 26 children (16 females and 10 males, median age: 6.2 years) with JIA before and after initiation of anti-TNFa or MTX therapy (median ± S.D.: 13.6 ± 6.6 months and 14.1 ± 4.5 months respectively, both groups n=13). Twenty demographically-matched controls were also included. Expression of FOXP3 was analyzed by flow cytometry and Real Time PCR. The relative expression of RORC2 was investigated on CD3+CD4+ sorted T cells. Surface expression of selectin L (CD62L) by gated CD4+FOXP3+ T cells was also evaluated. IL-17A on gated CD3+CD45RO+ memory T cells was assayed in PBMCs unstimulated and stimulated for 4 hrs with Phorbol Myristate Acetate (PMA) and Ionomycin. The expression of the activation marker CD69 on CD3+CD8+ and CD3+CD8- (representing CD4 T cells) was investigated to exclude the possibility that observed effects may be due to differences in T cell activation.
At baseline, the percentage of Tregs as well as the amount of FOXP3 mRNA were significantly reduced in JIA patients when compared with controls, confirming our previous results. A significant increase in the percentage of CD3+CD45RO+ memory T cells secreting IL-17A was found, upon activation with PMA and Ionomycin, in JIA patients when compared with controls (median %± S.D. 2.35 ± 0.8% vs 1.45 ± 0.77 %; P=0.0013). Interestingly, both these percentages changed, returning to that seen in controls, only in children who responded to anti-TNFa treatment. In contrast, the percentage of Tregs and Th17 cells remained unchanged in patients treated with MTX or unresponsive to anti-TNFa therapy and the same was true at transcriptional level. Furthermore, treatment with anti-TNFa and MTX did not produce significant changes in the percentage of CD3+CD69+ activated T cells. Of note, contrary to what has been observed in rheumatoid arthritis, no differences in the surface expression of CD62L by gated CD4+FOXP3+ T cells was noted after treatments with anti-TNFa and these levels were comparable to that detected in controls.
This study support an immunomodulatory effect of Etanercept and Adalimumab on Th17 and Treg cells, also suggesting a dominating Th17 responses in JIA children probably as a consequence of their peculiar immunological abnormalities.
To cite this abstract, please use the following information:
Olivito, Biagio, Simonini, Gabriele, Rossi, Gabriele, Betti, Letizia, Moriondo, Maria, de Martino, Maurizio, et al; AntiTnf Therapy, but Not Methotrexate (MTX), Affects the Balance Between CD4CD25FOXP3 Regulatory T Cells (Tregs) and Th17 Cells in Children with Juvenile Idiopathic Arthritis (JIA) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1311