Premature aging of the immune system in children with juvenile idiopathic arthritis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Prelog
Martina
M
Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria. Martina.Prelog@i-med.ac.at
Schwarzenbrunner
Nora
N
Sailer-Höck
Michaela
M
Kern
Hannelore
H
Klein-Franke
Andreas
A
Ausserlechner
Michael J
MJ
Koppelstaetter
Christian
C
Brunner
Andrea
A
Duftner
Christina
C
Dejaco
Christian
C
Strasak
Alexander M
AM
Müller
Thomas
T
Zimmerhackl
Lothar Bernd
LB
Brunner
Jürgen
J
D000375:Aging / Q000276:immunology*; D001171:Arthritis, Juvenile / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015870:Gene Expression; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D018655:Lymphocyte Count; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*
D019394:Ki-67 Antigen