NDT Advance Access published online on March 27, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl097
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1 Fifth Department of Medicine, University Hospital Mannheim, University of Heidelberg, Germany; S.M. and A.-I.K. contributed equally to this work
* To whom correspondence should be addressed. Background. Although in antineutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AASV) patients, activation of T-cells has been described, persistence of these alterations has not been well characterized. This study was conducted to define persistent T-cell activation (PTA) in AASV patients and to assess whether this correlates with disease activity, disease severity, age or therapy. Methods. The expression of CD4, CD45RO, CD25, CD26, CD28, CCR7 and HLA-DR was examined longitudinally in 38 consecutive AASV patients. Clinical parameters were compared by univariate and multiple analysis and Kaplan-Meier curves for relapse-free survival were calculated. Results. PTA could be defined as either of two activation phenotypes, i.e. a low percentage of CD4+ CD45RO- T-cells or a high percentage of CD25 in the naïve CD4+ population (n = 26), since only these phenotypes were stable over time and were not associated with active disease. In patients with PTA, major organ involvement was significantly more often found than in patients without PTA. Moreover, the cumulative cyclophosphamide dose (26.86 vs 8.53 P<0.01) was significantly increased in these patients, suggesting that PTA was associated with disease severity. In general, patients with PTA were older than those without (62.92±9.4 years vs 48.42±16.9 years respectively, P<0.01). PTA was independent of disease duration. Interestingly, patients with a low percentage of CD4+CD45RO- T-cells were significantly more often diagnosed as microscopic polyangiitis (P<0.01). Conclusion. We identified two independent phenotypes of T-cell activation in AASV patients. These phenotypes are persistent and do not reflect disease activity. PTA predominantly occurs in patients with severe disease. This might explain the higher cumulative cyclophosphamide dose found in these patients.
Received August 12, 2005
Accepted February 17, 2006
Original Article
Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis
Smaragdi Marinaki 1,
Anna-Isabelle Kälsch 1 *,
Peter Grimminger 2,
Annette Breedijk 2,
Rainer Birck 2,
Wilhelm H Schmitt 2,
Christel Weiss 3,
Fokko J van der Woude 2,
and
Benito A Yard 2
2 Fifth Department of Medicine, University Hospital Mannheim, University of Heidelberg, Germany
3 Department of Medical Statistics, University Hospital Mannheim, University of Heidelberg, Germany
Anna-Isabelle Kälsch, E-mail: anna-isabelle.kaelsch{at}med5.ma.uni-heidelberg.de
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