NDT Advance Access originally published online on March 27, 2006
Nephrology Dialysis Transplantation 2006 21(7):1825-1832; doi:10.1093/ndt/gfl097
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Persistent T-cell activation and clinical correlations in patients with ANCA-associated systemic vasculitis
Fifth Department of Medicine and 1 Department of Medical Statistics University Hospital Mannheim, University of Heidelberg, Germany.
Correspondence and offprint requests to: Anna-Isabelle Kälsch, MD, Fifth Department of Medicine, (Nephrology/Endocrinology/Rheumatology), University Hospital Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68135 Mannheim, Germany. Email: anna-isabelle.kaelsch{at}med5.ma.uni-heidelberg.de
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.
Keywords: ANCA-associated vasculitis; clinical correlation; persistence; T-cell activation
*S.M. and A.-I.K. contributed equally to this work
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