Thymic function in juvenile idiopathic arthritis

被引:19
作者
Lorenzi, A. R. [1 ]
Morgan, T. A. [1 ]
Anderson, A. [1 ]
Catterall, J. [1 ]
Patterson, A. M. [1 ]
Foster, H. E. [1 ]
Isaacs, J. D. [1 ]
机构
[1] Univ Newcastle, Musculoskeletal Res Grp, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
关键词
STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD; MULTIPLE-SCLEROSIS; HIV-INFECTION; NAIVE; RECONSTITUTION; REPERTOIRE;
D O I
10.1136/ard.2008.088112
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Thymic function declines exponentially with age. Impaired thymic function has been associated with autoimmune disease in adults but has never been formally assessed in childhood autoimmunity. Therefore, thymic function in children with the autoimmune disease juvenile idiopathic arthritis (JIA) was determined. Methods: Thymic function was measured in 70 children and young adults with JIA (age range 2.1-30.8 (median 10.4)) and 110 healthy age-matched controls using four independent assays. T cell receptor excision circles (WBLogTREC/ml) and the proportion of CD4(+) CD45RA(+)CD31(+) T cells (representing recent thymic emigrants; %RTEs) were quantified and intrathymic proliferation measured by calculating the alpha TREC/Sigma beta TREC ratio. Lastly, regulatory T cells (T-Reg) of thymic origin (CD4(+)FOXP3(+)) were quantified in peripheral blood to assess the ability of the thymus in JIA to generate this T cell subset. Results: Thymic function was equivalent by all four parameters in JIA when compared with the control population. Furthermore, there was no consistent effect of JIA subtype on thymic function, although intrathymic proliferation was higher in the small rheumatoid factor (RF)(+) polyarticular group. There were no significant effects of disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids on thymic function, although those with the worst prognostic ILAR (International League of Associations for Rheumatology) subtypes were also those most likely to be on a DMARD. Conclusions: It is demonstrated that children and young adults with JIA, unlike adults with autoimmune diseases, have thymic function that is comparable with that of healthy controls. The varied pathologies represented by the term "JIA'' suggest this observation may not be disease specific and raises interesting questions about the aetiology of thymic impairment in adult autoimmunity.
引用
收藏
页码:983 / 990
页数:8
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  • [1] Aspinall R, 2001, Dev Immunol, V8, P95, DOI 10.1155/2001/17064
  • [2] The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3
    Bennett, CL
    Christie, J
    Ramsdell, F
    Brunkow, ME
    Ferguson, PJ
    Whitesell, L
    Kelly, TE
    Saulsbury, FT
    Chance, PF
    Ochs, HD
    [J]. NATURE GENETICS, 2001, 27 (01) : 20 - 21
  • [3] High-dose cyclophosphamide with stem cell rescue for severe rheumatoid arthritis: short-term efficacy correlates with reduction of macroscopic and histologic synovitis
    Bingham, S
    Veale, D
    Fearon, U
    Isaacs, JD
    Morgan, G
    Emery, P
    McGonagle, D
    Reece, R
    Clague, R
    Snowden, JA
    [J]. ARTHRITIS AND RHEUMATISM, 2002, 46 (03): : 837 - 839
  • [4] Naive CD4+ T cells and recent thymic emigrant levels in treated individuals with HIV:: Clinical relevance
    Bofill, Margarita
    Martinez-Picado, Javier
    Ruiz-Hernandez, Raul
    Cabrera, Cecilia
    Marfil, Silvia
    Erkizia, Itziar
    Bellido, Rocio
    Romeu, Joan
    Clotet, Bonaventura
    Ruiz, Lidia
    [J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 2006, 22 (09) : 893 - 896
  • [5] Autologous stem cell transplantation in children with severe progressive systemic or polyarticular juvenile idiopathic arthritis - Long-term followup of a prospective clinical trial
    Brinkman, D. M. C.
    de Kleer, I. M.
    ten Cate, R.
    van Rossum, M. A. J.
    Bekkering, W. P.
    Fasth, A.
    van Tol, M. J. D.
    Kuis, W.
    Wulffraat, N. M.
    Vossen, J. M.
    [J]. ARTHRITIS AND RHEUMATISM, 2007, 56 (07): : 2410 - 2421
  • [6] Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network
    de Kleer, I
    Vastert, B
    Klein, M
    Teklenburg, G
    Arkesteijn, G
    Yung, GP
    Albani, S
    Kuis, W
    Wulffraat, N
    Prakken, B
    [J]. BLOOD, 2006, 107 (04) : 1696 - 1702
  • [7] HIV infection rapidly induces and maintains a substantial suppression of thymocyte proliferation
    Dion, ML
    Poulin, JF
    Bordi, R
    Sylvestre, M
    Corsini, R
    Kettaf, N
    Dalloul, A
    Boulassel, MR
    Debré, P
    Routy, JP
    Grossman, Z
    Sékaly, RP
    Cheynier, R
    [J]. IMMUNITY, 2004, 21 (06) : 757 - 768
  • [8] Changes in thymic function with age and during the treatment of HIV infection
    Douek, DC
    McFarland, RD
    Keiser, PH
    Gage, EA
    Massey, JM
    Haynes, BF
    Polis, MA
    Haase, AT
    Feinberg, MB
    Sullivan, JL
    Jamieson, BD
    Zack, JA
    Picker, LJ
    Koup, RA
    [J]. NATURE, 1998, 396 (6712) : 690 - 695
  • [9] Reconstitution of the T-cell compartment after bone marrow transplantation: Restoration of the repertoire by thymic emigrants
    Dumont-Girard, F
    Roux, E
    van Lier, RA
    Hale, G
    Helg, C
    Chapuis, B
    Starobinski, M
    Roosnek, E
    [J]. BLOOD, 1998, 92 (11) : 4464 - 4471
  • [10] Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children
    Eyrich, M
    Wollny, G
    Tzaribaschev, N
    Dietz, M
    Brügger, D
    Bader, P
    Lang, P
    Schilbach, K
    Winkler, B
    Niethammer, D
    Schlegel, PG
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2005, 11 (03) : 194 - 205