Premature aging of the immune system in children with juvenile idiopathic arthritis
Article first published online: 24 JUN 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 7, pages 2153–2162, July 2008
How to Cite
Prelog, M., Schwarzenbrunner, N., Sailer-Höck, M., Kern, H., Klein-Franke, A., Ausserlechner, M. J., Koppelstaetter, C., Brunner, A., Duftner, C., Dejaco, C., Strasak, A. M., Müller, T., Zimmerhackl, L. B. and Brunner, J. (2008), Premature aging of the immune system in children with juvenile idiopathic arthritis. Arthritis & Rheumatism, 58: 2153–2162. doi: 10.1002/art.23599
- Issue published online: 24 JUN 2008
- Article first published online: 24 JUN 2008
- Manuscript Accepted: 27 MAR 2008
- Manuscript Received: 4 MAY 2007
- Medical Research Fund Tyrol. Grant Number: MFF Tirol project 105
- Tyrolean Science Fund. Grant Number: TWF project 2006-2-425
- Dr. Kolassa Rheumatology Award 2005
Juvenile idiopathic arthritis (JIA) is an autoimmune disease of the young. The pathogenesis is not completely understood. Premature aging, associated thymic involution, and compensatory autoproliferation could play important roles in the pathogenesis of autoimmunity. We undertook this study to determine whether patients with JIA demonstrate premature immunosenescence.
To test this hypothesis, we measured 3 indicators of aging: the percentages and total counts of peripheral blood naive T cells, the frequency of T cell receptor excision circles (TRECs) in naive T cells, and telomeric erosion and Ki-67 expression as estimates of the replicative history of homeostatic proliferation.
JIA patients showed an accelerated loss of CD4+,CD45RA+,CD62L+ naive T cells with advancing age and a compensatory increase in the number of CD4+,CD45RO+ memory T cells. JIA patients demonstrated a significantly decreased frequency of TRECs in CD4+,CD45RA+ naive T cells compared with age-matched healthy donors (P = 0.002). TREC numbers correlated with age only in healthy donors (P = 0.0001). Telomeric erosion in CD4+,CD45RA+ naive T cells was increased in JIA patients (P = 0.01). The percentages of Ki-67–positive CD4+,CD45RA+ naive T cells were increased in JIA patients (P = 0.001) and correlated with disease duration (P = 0.003), which was also an independent factor contributing to telomeric erosion (P = 0.04).
Our findings suggest that age-inappropriate T cell senescence and disturbed T cell homeostasis may contribute to the development of JIA. In patients with JIA, dysfunction in the ability to reconstitute the T cell compartment should be considered when exploring new therapeutic strategies.