NDT Advance Access published online on February 4, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp019
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Dendritic cells in renal biopsies of patients with ANCA-associated vasculitis
1 Division of Clinical and Experimental Immunology, Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands 2 Department of Nephrology, University Duisburg-Essen, Essen, Germany
Correspondence and offprint requests to: Jan Willem Cohen Tervaert, Division of Clinical and Experimental Immunology, Department of Internal Medicine, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands. Tel: +31-43-3881433; Fax: +31-43-3884164; E-mail: Secretariaat-IMMUNO{at}IMMUNO.unimaas.nl
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Abstract |
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Background. Dendritic cells (DCs) maintain immune tolerance and are able to initiate immune responses. Their involvement in ANCA-associated vasculitis (AAV) is unknown. In this study, the participation of DC subsets is investigated in renal biopsies of AAV patients.
Method. A total of 25 patients with biopsy-proven AAV and five healthy controls (HC) with normal renal histology were included. Renal biopsies were stained for mature (CD208), immature (CD209), plasmacytoid (CD303) and Langerhans (CD1a) DC subsets. Furthermore, T-cells were stained using a T-cell marker (CD3). The interstitial cellular infiltrate was graded semi-quantitatively from 0+ (= absence of cells) to 3+ (= numerous cells). Within the glomeruli, an absolute count was performed for positive cells.
Results. CD208+ and CD209+ cells were found within patients’ glomeruli but not in HC (1 ± 0.3 versus 0.08 ± 0.1 cells/glom; 2 ± 0.3 versus 0.1 ± 0.07 cells/glom). An average of 0.3 ± 0.1 cell/glom expressed CD3 in patients while few cells were found in HC (0.1 ± 0.7 cell/glom). Focal interstitial cellular infiltrates were observed in patients’ biopsies but not in HC. Interstitial infiltration with CD3+ and CD209+ cells was assessed at an average of 1+, but some glomeruli and tubuli were surrounded by CD3+ and CD209+ cells forming clusters. Serial sections revealed that CD209+ cells were present in CD3+ rich areas.
Conclusion. Both mature and immature glomerular DCs are found in renal biopsies of patients with AAV. Immature DCs cluster with T-cells in interstitial infiltrates in these biopsies. Since DCs form aggregates in T-cell areas, we hypothesize that these cells interact with each other and are involved in lymphoid neogenesis.
Keywords: ANCA; AAV; dendritic cells; Wegener’s Granulomatosis
Received for publication: 5. 5.08
Accepted in revised form: 12. 1.09