Characterization of interstitial infiltrates in MPO and PR3 anti-neutrophil cytoplasmic antibody glomerulonephritis.

INTRODUCTION: It has been recognized that T cells have a pathogenic role in anti-neutrophil cytoplasmic antibody- (ANCA) associated vasculitis, in addition to being dominant cells in the interstitium in ANCA glomerulonephritis (GN). Given there are differences in renal outcomes based on ANCA type, we sought to characterize the interstitial infiltrate in ANCA GN to determine differences in relation to ANCA type and renal function. METHODS: Immunohistochemistry stains for CD3, CD4, CD20, C4d and FOXP3 were done in renal biopsies of patients with ANCA GN. Light microscopy was used to determine the percentage of cortical interstitium containing positive cells. Demographics, ANCA type and entry eGFR were recorded. The level of staining was compared between ANCA type and entry eGFR using Wilcoxon rank-sum test. RESULTS: Renal biopsies of 16 patients with MPO and 14 with PR3 ANCA GN were studied. CD3 cells were the predominant cells, with all biopsies staining positive for CD4 and FOXP3. C4d staining was negative in all biopsies, with no significant difference in staining between MPO and PR3 groups for any of the identified cell types. However, regardless of ANCA type, FOXP3 staining was significantly higher in patients with baseline GFR < 10 compared with GFR > 10 mL/min/1.73 m2(mean 7.54, SD 6.6 versus mean 2.67, SD 3.6; p = 0.04). CONCLUSION: These data confirm the role of T cells in ANCA GN and demonstrate no differences in interstitial T and B cell infiltrates between PR3 and MPO ANCA GN. Higher FOXP3 signal associates with lower renal function, suggesting a role for regulatory T cells. Further characterization of this T cell subset should be explored in future studies.

Serum cytokine and chemokine levels in patients with eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, or eosinophilic asthma.

OBJECTIVES: The pathogenesis of eosinophilic granulomatosis with polyangiitis (EGPA) remains poorly understood, and may overlap with eosinophilic asthma and primary hypereosinophilic syndrome (HES). The aim of this study was to analyse a panel of serum cytokines and chemokines as markers of disease activity in patients with these conditions. METHODS: The levels of 54 cytokines and chemokines were measured in the sera of 40 patients with active EGPA, 10 of these patients during inactive disease, 6 patients with HES, 8 with asthma, and 10 healthy controls. Serum cytokine/chemokines measured included interleukin (IL)-1α, 1ß, 3, 4, 5, 6, 8, 13, 15, 17A, 17E(25), 18, 23 and 33, soluble IL-2 receptor alpha, eotaxin-1 (CCL11), -2 (CCL24) and -3 (CCL26), macrophage-derived chemokine (MDC/CCL22), macrophage inflammatory protein (MIP)-1a and -1b, and tumour necrosis factor (TNF)-α. Results were compared between disease and control groups using regression analysis, with Bonferroni correction for multiple comparisons (significant p value ≤0.00093). RESULTS: Significant differences were observed only in serum levels of MDC, IL-8, MIP-1a and -1b, TNF-α, each of which were lower in patients with active EGPA than in healthy controls (p<0.0001). Differences between patients with active disease and other disease groups did not reach significance. Paired comparisons between sera from patients with active or inactive EGPA showed no significant difference for any of the studied cytokines or chemokines. CONCLUSIONS: No clear difference in the serum levels of measured cytokines and chemokines helped distinguish between active EGPA or inactive EGPA, or other disease or control groups.

Levamisole monotherapy for oral lichen planus.

BACKGROUND: Several different kinds of drugs have been used to treat chronic oral lichen planus (OLP). During the last decade, there have been several reports demonstrating success with levamisole and low dose prednisolone therapy for treating OLP. However, some OLP patients who have underlying diseases such as diabetes, hypertension and malignancy are unable to take steroids. OBJECTIVE: The aim of this study was to evaluate levamisole monotherapy for treating OLP. METHODS: Eleven patients who had OLP were treated with levamisole between 2005 and 2007. The levamisole was administered at a dose 50 mg thrice daily for three consecutive days, but then it was not administered on the following four days. RESULTS: After 2 weeks of treatment, 8 patients reported a partial response, 3 patients reported no response and no patients reported clearance of lesion. After 4 weeks of treatment, 6 patients reported a partial response, 3 patients reported no response and 2 patients reported clearance of lesion. Furthermore, after 3 months of treatment, 3 patients reported a partial response, 3 patients reported no response and 5 patients reported complete clearance of lesion. Clinical improvement was shown in 2 weeks, whilst the mean duration to achieve clearance of lesion was 6.2 weeks. Although 1 patient had mild itching, there were no significant adverse effects. CONCLUSION: Levamisole monotherapy could be a successful and safe treatment option for patients with chronic OLP and who cannot take steroids.