Abstract
Purpose: The CD40/CD40 ligand (CD40L) system is associated with pathogenic processes of inflammatory diseases, and elevated levels of soluble CD40L have been observed in sera from patients with autoimmune diseases. To determine the diagnostic value of serum-soluble CD40L in Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), we investigated patients with MPO-AAV at various stages of the disease. Methods: Twenty-eight samples were from patients with active MPO-AAV: 28 samples from inactive-vasculitis patients without infection and 16 samples from inactive-vasculitis patients with infectious complications. Serum soluble CD40L was measured by an enzyme-linked immunosorbent assay. Serum-soluble CD40L was also measured in 15 patients with infectious diseases and in 28 control subjects. Results: The serum-soluble CD40L level was higher in the patients with inactive vasculitis with infectious complications than in those with inactive vasculitis without infection and the normal control, but there was no significant difference in CD40L levels between the patients with active vasculitis and those with inactive vasculitis with infectious complications. There were significant correlations between the serum levels of soluble CD40L and the serum creatinine and CRP levels. The serum soluble CD40L/creatinine ratio was higher in the inactive vasculitis with infectious complications group than in the active vasculitis group, inactive vasculitis without infection group and the normal control. Comparative receiver-operating-characteristic curves showed that this ratio had 92.8% sensitivity and 96.8% specificity for differentiating patients with infection from those without infection. Conclusion: Serum-soluble CD40L was not associated with disease activity, but it may be a useful marker for the detection of infectious complications in MPO-AAV.
Highlights
In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the diagnostic value of assays for ANCAs is widely accepted
Elevated levels of soluble CD40 and its ligand (CD40L) have been observed in sera from patients with systemic lupus erythematosus (SLE) [7,8], rheumatoid arthritis with vasculitis [9], Sjögren’s syndrome [8], mixed connective tissue disease [10], systemic sclerosis [11] and Kawasaki disease [12], and a direct relationship can be seen between serumsoluble CD40L and the disease severities or titers of autoantibodies [7] and rheumatoid factor [8]
We hypothesized that CD40L may be released from T cells or damaged tissue in AAV, and in the present study we investigated patients with micropolyangiitis (MPA) at various stages of the disease to determine the diagnostic value of serum-soluble CD40L in MPOAAV
Summary
In antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the diagnostic value of assays for ANCAs is widely accepted. ANCAs can activate cytokine-primed neutrophils, causing an oxidative burst, degranulation, the release of inflammatory cytokines, and damage to endothelial cells in vitro [1], and an intravenous injection of mouse antibodies specific for mouse MPO induced pauci-immune necrotizing and crescentic glomerulonephritis in a mouse model that closely mimics the human disease [2]. Elevated levels of soluble CD40L have been observed in sera from patients with systemic lupus erythematosus (SLE) [7,8], rheumatoid arthritis with vasculitis [9], Sjögren’s syndrome [8], mixed connective tissue disease [10], systemic sclerosis [11] and Kawasaki disease [12], and a direct relationship can be seen between serumsoluble CD40L and the disease severities or titers of autoantibodies (anti-double-strand DNA antibody) [7] and rheumatoid factor [8]. In patients with granulomatosis with polyangiitis (GPA), soluble CD40L was associated with disease activity [13]
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