title: Premature aging of the immune system in children with juvenile idiopathic arthritis.
abstract: 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.
authors.affiliation: Department of Pediatrics, Medical University Innsbruck, Innsbruck, Austria. Martina.Prelog@i-med.ac.at
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog
authors.forename: Nora
authors.initials: N
authors.lastname: Schwarzenbrunner
authors.forename: Michaela
authors.initials: M
authors.lastname: Sailer-Höck
authors.forename: Hannelore
authors.initials: H
authors.lastname: Kern
authors.forename: Andreas
authors.initials: A
authors.lastname: Klein-Franke
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ausserlechner
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.forename: Andrea
authors.initials: A
authors.lastname: Brunner
authors.forename: Christina
authors.initials: C
authors.lastname: Duftner
authors.forename: Christian
authors.initials: C
authors.lastname: Dejaco
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Strasak
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Lothar Bernd
authors.initials: LB
authors.lastname: Zimmerhackl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brunner
mesh_terms: 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*
chemical_list: D019394:Ki-67 Antigen