Autoantibodies against glomerular endothelial cells in anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis.

AIM: The prevalence of anti-endothelial cell autoantibodies (AECA) in patients with anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis (ASV) has been reported by several groups with conflicting results ranging from 8% to 100%. Types of substrate cells used for AECA testing partially explain this variation. Endothelial cells from kidney origin have been reported to be predominant in AECA binding. Therefore, we investigated AECA prevalence using a human glomerular endothelial cell line compared with primary human umbilical vein endothelial cells, which have frequently been used for AECA detection. METHODS: Sera from 43 ASV patients (29 Wegener's granulomatosis (WG), 14 microscopic polyangiitis (MPA)) with active disease were assessed for AECA positivity using cell-based enzyme-linked immunosorbent assay. Forty serum samples from healthy controls were tested in parallel. To evaluate endothelial activation levels, soluble intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 were measured with capture enzyme-linked immunosorbent assay. RESULTS: The AECA were detected in 4 of 29 WG patients (14%), but none of 14 MPA patients was positive for AECA using glomerular endothelial cell as a substrate, whereas AECA were positive in 10% of WG patients and 14% of MPA patients on human umbilical vein endothelial cells. No significant differences were found between ASV patients and controls in AECA test. Serum levels of vascular cell adhesion molecule-1 and soluble intercellular cell adhesion molecule-1 in ASV patients were significantly higher than in controls. However, there were no differences between AECA-positive and -negative patients for both of the activation markers. CONCLUSION: The AECA, directed against glomerular endothelial cells, have a low prevalence in ASV patients with active disease and are not correlated with endothelial activation.

Cytokine responses to stimulation of whole blood from patients with Buruli ulcer disease in Ghana.

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, follows an indolent course of initial progression to ulceration accompanied by extensive tissue damage. It has been suggested that healing disease stages are accompanied by a protective immune response. We hypothesized that interleukin-4 (IL-4)- or IL-10-induced downregulation of Th-1 responses plays a key role in the progression of early BUD and that healing is accompanied by an augmented Th-1 response. Gamma interferon (IFN-gamma), IL-4, and IL-10 responses were measured after in vitro stimulation with phytohemagglutinin (PHA) and tuberculin purified protein derivative (PPD) of whole blood from 39 (23 early- and 16 late-stage) BUD patients and 39 healthy control subjects in Ghana. Additionally, 30 patients with active or treated tuberculosis (TB) serving as PPD-responsive positive controls were studied. Early-stage BUD patients produced significantly lower levels of IFN and IFN-gamma/IL-4 ratios compared to late-stage BUD patients after PHA stimulation. Compared to that of controls, IFN-gamma production after tuberculin stimulation was significantly higher in late-stage but not in early-stage BUD patients (P=0.009). IL-10 and IL-4 levels did not differ between BUD patients and controls, although active TB patients had significantly higher IL-10 production levels than did treated TB patients. Multivariate analysis showed no confounding factors. In conclusion, Th-1 down regulation in early BUD appears to reverse in later stages of BUD, although an association with IL-10 or IL-4 production does not emerge from our data. Here we show differences in Th-1-type cytokine production between early- and late-stage BUD that might reflect an improved immune defense over time.