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Objectives. The chemokine CXCL13, also known as BCA-1 (B-cell-attracting chemokine-1) or BLC (Blymphocyte 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

B-cell depletion with rituximab, a chimeric anti-CD20 antibody, is a novel treatment for refractory and relapsing ANCA-associated small-vessel vasculitis. Data are limited and most reports describe single patients or small numbers of patients followed prospectively.We report a single-centre experience with 15 patients who received rituximab for refractory or relapsing ANCA-associated vasculitis. All patients had been treated with corticosteroids and cyclophosphamide and a variety of other second-line immunosuppressive agents. None of the patients had evidence of infection and received four infusions of 375 mg/m(2) of rituximab. Disease activity was assessed in accordance with the Birmingham Vasculitis Activity Score (BVAS). BVAS, C-reactive protein and ANCA titres were recorded at baseline and during follow-up.B-cell depletion was achieved in all patients. Partial or complete remission was seen in 14 of 15 patients with a significant decline in BVAS compared to baseline (P0.007). One patient with granulomatous ANCA-associated vasculitis did not respond to rituximab. There were no side effects during rituximab infusion. Transient leucopenia was observed in two patients. One patient with bronchial stenosis died of pneumonia 5.5 months after the initiation of rituximab treatment. One initially anti-HBc-positive/HBsAg-negative patient experienced a reactivation of hepatitis B, developed end-stage renal failure and died after refusal of dialysis.We report the largest case series of rituximab use for ANCA-associated vasculitis so far. Our data support that the drug is capable of inducing partial or complete remission in refractory or relapsing patients. Leucopenia and infectious complications remain a matter of concern.

During the last decade, circulating endothelial cells (CECs) have been used as a surrogate marker of endothelial damage in a variety of vascular disorders. The severely damaged phenotype of CECs in vasculitis led to the hypothesis that such circulating apoptotic and/or necrotic debris may itself be a mediator of disease. Very recently, first evidence has emerged to support this assumption [1]. The aim of this editorial comment is to provide a brief review of CECs, describe clinical applications with an emphasis on renal disease, and put the new pathogenetic findings into perspective. We also suggest further avenues of research.

Accelerated arteriosclerosis with cardiovascular disease is the main cause of death in end-stage renal disease patients. Increased, levels of C-reactive protein (CRP) and evidence of chronic Chlamydia pneumoniae infection have been identified as risk factors for cardiovascular disease in the general population. We tested the hypothesis that elevation of CRP, indicating chronic inflammation, and positive serum antibody titres for C. pneumoniae are associated with an increased cardiovascular mortality in patients on chronic peritoneal dialysis.We measured CRP and antibodies to C. pneumoniae in 34 patients on peritoneal dialysis. CRP was measured by a sensitive ELISA and C. pneumoniae antibodies by microimmunofluorescence. In addition, risk factors such as lipids, smoking status and hypertension were assessed. Coronary artery disease (CAD) was defined by cardiac stress testing and/or angiography. Patients showing clinical evidence of systemic or peritoneal dialysis-associated infection during the investigation period of 6 months (between 1990 and 1991) were excluded.The incidence of CAD was significantly increased in patients with CRP values1.5 mg/l (odds ratio 7.0, P0.022) during 72 months of follow-up. In addition, in patients seropositive for IgA C. pneumoniae antibodies, the incidence of CAD was significantly increased (odds ratio 7.2, P0.014). These findings resulted in an increased risk of death in patients with mean CRP values1.5 mg/l at the start of the study (odds ratio 20.0, P0.001). Furthermore, in patients seropositive for IgA C. pneumoniae antibodies, the risk of death (odds ratio 10.2, P0.005) was significantly increased. There was a highly significant correlation between CRP and seropositivity for IgA C. pneumoniae antibodies (r=0.445, P0.01).Increased circulating CRP and seropositivity for C. pneumoniae in patients on chronic peritoneal dialysis are associated with reduced survival due to cardiovascular complications. CRP and C. pneumoniae antibodies may indicate a chronic inflammatory process as an underlying cause and/or result of arteriosclerosis.

Background. The activation of neutrophils and monocytes by ANCA, resulting in the release of reactive oxygen species and proteases like myeloperoxidase (MPO), is essential to the pathogenesis of ANCAassociated vasculitis. As the A allele of the G-463A MPO gene polymorphism is associated with diminished activity of MPO, it is conceivable that the presence of this allele protects against MPO–ANCAassociated vasculitis. Methods. Allelic frequencies of the G-463A polymorphism were studied in 119 ANCA-associated vasculitis patients, 48 with MPO–ANCA and 71 with proteinase 3 (PR3)–ANCA. Results. Allelic frequencies of MPO G-463A promoter polymorphism did not differ between MPO–ANCAand PR3–ANCA-associated vasculitis patients. Moreover, allelic distribution was similar to that of the normal population. Conclusions. The data suggest that G-463A polymorphism does not seem to contribute to either MPO–ANCA- or PR3–ANCA-associated vasculitis formation.

Circulating endothelial cells (CECs) were first detected in the 1970s although convenient techniques to isolate them have only recently become available [1]. These cells have now been shown to be present in a variety of vascular disorders but only a few reports have appeared since the mid-1990s. Very recently we were able to demonstrate grossly elevated numbers of CECs as a novel marker of disease activity in patients with ANCA-associated vasculitis [2]. It appears that this approach to vascular injury has not been appreciated so far and that its use should be evaluated in other vascular disorders as well.

In this study serum C-reactive protein values were measured to prove the induction of an acute-phase response during the haemodialysis procedure in end-stage renal disease patients. C-reactive protein values were measured with a sensitive enzyme-linked immunosorbent assay to detect values below the detection limit of standard assays. Predialysis C-reactive protein serum values in 17 patients on regular haemodialysis with cuprophan dialysers were greater than those of 18 normal controls (P less than 0.001). In the same group of haemodialysis patients serum C-reactive protein values 24 h after haemodialysis were significantly greater than predialysis values (P less than 0.001). These results suggest that acute-phase proteins are induced during haemodialysis, probably due to cytokine release during the haemodialysis procedure.

Background In patients with ANCA-associated vasculitis the frequent development of relapses after successful initial treatment remains a major therapeutic problem. Thus a long-term prophylactic therapy with low side-effect potential is needed. As recent data suggest an involvement of T cells in the pathogenesis of ANCA-associated vasculitis, the prophylactic value of therapy with low-dose cyclosporin was investigated in seven patients (three with Wegener's granulomatosis, four with microscopic polyangiitis, all with renal involvement) who had developed at least one relapse during cyclophosphamide (CP) treatment or in the first 4 months after the end of CP therapy. Methods After remission had been achieved for 6 months using CP and prednisolone, the CP dose was reduced (3 months 75%, 3 months 50%) and cyclosporin was added concomitantly (dose adjusted to whole blood levels 60-90 ng/ml). Cyclosporin therapy was continued for 1 year after the end of CP treatment. Results During a mean follow-up of 24 months no patient developed a relapse. Two patients developed a herpes zoster infection. No severe bacterial infection occurred. Conclusions These preliminary results indicate that cyclosporin can be successfully used to sustain remission in patients with a relapsing course of ANCA-associated vasculitis and renal involvement.