Rheumatology 2003; 42: 375-379
© 2003 British Society for Rheumatology
Paediatric Rheumatology |
Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation
Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands
Abstract
Objectives. Familial haemophagocytic lymphohistiocytosis (FHL) is a disorder characterized by deficient cytotoxic T-cell function and activated macrophages, owing to a defect in the perforin gene and absent perforin expression. Because symptoms of patients with systemic juvenile idiopathic arthritis (sJIA) are sometimes clinically very similar to those with FHL, we studied whether perforin expression in sJIA patients would be reduced also.
Methods. We determined the perforin expression levels on two subsets of CD8+ cells (CD8+CD28-CD45RA- and CD8+CD28-CD45RA+) and natural killer (NK) cells from patients with sJIA under conventional treatment as well as before and after autologous stem-cell transplantation (ASCT).
Results. CD45RA- cytotoxic effector cells of sJIA patients (n=13) express significantly lower levels of perforin than polyarticular juvenile idiopathic arthritis (pJIA, n=9) patients [sJIA mean fluorescence intensity (MFI) 34.6; pJIA MFI 98.0] or control donors (MFI 124.6, n=5). A similar pattern was seen in the CD45RA+ subset. Also NK cells from sJIA patients expressed significantly less intracellular perforin (sJIA MFI 398.4; controls MFI 972.4). In four patients with sJIA who were treated with ASCT, a clear increase in perforin expression was found at 12 months after ASCT in both cytotoxic effector cell subsets (CD45RA- subset before ASCT MFI 13.2; 12 months after ASCT MFI 172.3).
Conclusion. We conclude that perforin expression can be severely reduced in sJIA. This finding may implicate defective cytotoxicity and haemophagocytosis and could thus explain why sJIA may be complicated by macrophage activation syndrome. ASCT leads to a reconstitution of the (T cell) immune system with a normal expression of perforin.
KEY WORDS: Perforin expression, Juvenile idiopathic arthritis, Stem-cell transplantation.
Notes
Correspondence to: N. M. Wulffraat. E-mail: n.wulffraat{at}wkz.azu.nl
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Frosch and J. Roth New insights in systemic juvenile idiopathic arthritis--from pathophysiology to treatment Rheumatology, February 1, 2008; 47(2): 121 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-B Arlet, D Le Thi Huong, A Marinho, Z Amoura, B Wechsler, T Papo, and J-C Piette Reactive haemophagocytic syndrome in adult-onset Still's disease: a report of six patients and a review of the literature Ann Rheum Dis, December 1, 2006; 65(12): 1596 - 1601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. de Kleer, B. Vastert, M. Klein, G. Teklenburg, G. Arkesteijn, G. P. Yung, S. Albani, W. Kuis, N. Wulffraat, and B. Prakken Autologous stem cell transplantation for autoimmunity induces immunologic self-tolerance by reprogramming autoreactive T cells and restoring the CD4+CD25+ immune regulatory network Blood, February 15, 2006; 107(4): 1696 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Ramanan and A. A. Grom Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology, November 1, 2005; 44(11): 1350 - 1353. [Abstract] [Full Text] [PDF]
|
|