Elevated production of serum B-cell-attracting chemokine-1 (BCA-1/CXCL13) is correlated with childhood-onset lupus disease activity, severity, and renal involvement

Objectives. Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease in which cytokines such as B lymphocyte chemoattractant (BLC) or CXC motif ligand 13 (CXCL13) play an important role as major regulators of B1 and B2 cell trafficking for activation of autoreactive T helper cells. CXCL13 can induce trafficking of the CXCR5+ T lymphocyte subset designated as follicular helper T lymphocytes which are specifically involved in autoantibody production during the development of lupus. Here, we ask whether serum levels of CXCL13 correlate with disease activity and severity and renal involvement in children with SLE. Methods. Serum samples from 40 children with SLE and 32 healthy controls were analyzed by ELISA for the concentrations of CXCL13. Results. Median (inter-quartile range (IQR) serum CXCL13 concentrations (pg/ml) were increasingly higher across the following groups: healthy controls (71.6 (66.6-81.8), SLE patients with inactive disease (140.8 (99.7-198.8), p = 0.0005 versus controls) and active disease (293.0 (105.5-489.8), p = 0.0001 versus controls) (inactive versus active; p < 0.0001). Concentrations of circulating CXCL13 correlated with SLEDAI (r = 0.499, p = 0.029) and double-stranded DNA titers (r = 0.71, p < 0.001). Moreover, median CXCL13 concentrations were higher in patients with renal involvement (270.6 (150.4-430.7) compared with those without renal involvement (120.6 (70.5-208.9). According to WHO pathological classification of lupus nephritis, median CXCL13 concentrations were higher in children with class III, IV and V nephritis compared with those with class I and II nephritis (333.9 (169.4-491.5) versus (180.4 (107.9-209.7). Conclusions. Our data indicate that an increased level of CXCL13 is a feature of SLE that correlates with disease activity and severity. CXCL13 expression in lupus nephritis represents a new pathogenetic mechanism of diagnostic and prognostic significance. The pharmacological regulation of CXCL13 and its receptor, CXCR5, expression may be a useful tool in the therapy of lupus nephritis. Lupus (2011) 20, 845-854.