NDT Advance Access published online on July 13, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp343
B-cell-attracting chemokine CXCL13 as a marker of disease activity and renal involvement in systemic lupus erythematosus (SLE)
1 Department of Medicine/Nephrology, Hannover Medical School 2 Nephrological Center, Medical Policlinic, University of München, Pettenkoferstr. 8a, 80336, München 3 Department of Medicine/Clinical Immunology and Rheumatology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany
Correspondence and offprint requests to: Lena Schiffer; E-mail: schiffer.lena{at}mh-hannover.de
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Abstract |
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Objectives. The chemokine CXCL13, also known as BCA-1 (B-cell-attracting chemokine-1) or BLC (B-lymphocyte chemoattractant), is a major regulator of B-cell trafficking. We have recently shown that excessive expression of dendritic cell-derived CXCL13 is a distinctive early event for nephritis in a murine model of systemic lupus erythematosus (SLE). Furthermore, in kidney biopsies from SLE patients, CXCL13 protein and mRNA are strongly expressed in B-cell-containing inflammatory lesions. Here, we ask whether serum levels of CXCL13 correlate with disease activity and renal involvement in SLE patients.
Methods. CXCL13 was measured in sera obtained from 91 patients with SLE and 40 healthy controls by ELISA methodology. Disease activity was calculated according to the SLE Disease Activity Index (SLEDAI).
Results. Median (IQR) serum CXCL13 concentrations were increasingly higher across the following groups: healthy controls [31.6 (26.8–41.3) pg/ml], SLE patients with inactive disease (SLEDAI <6) [68.2 (27.8–133.0) pg/ml, P = 0.0006 versus controls] and active disease [196.0 (75.9–416.8) pg/ml, P = 0.0001 versus controls] (inactive versus active P < 0.0001). Concentrations of circulating CXCL13 correlated with SLEDAI (r = 0.56, P < 0.0001) and double-stranded DNA titres (r = 0.36, P < 0.0005). Moreover, median CXCL13 concentrations were higher in patients with renal involvement [175.5 (105.3–422.6) pg/ml] compared to those without renal involvement [82.1 (42.9–219.8) pg/ml].
Conclusions. Our data indicate that increased level of CXCL13 is a feature of SLE that correlates with disease activity. Furthermore, CXCL13 might be a readily available surrogate marker to monitor the extent of aberrant B-cell (dys-)function.
Keywords: B cells; biomarker; chemokines; CXCL13; lupus nephritis
* Authors contributed equally.
Received for publication: 24.11.08
Accepted in revised form: 22. 6.09