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Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and
Ruth J Pepper1, Sally Hamour, Konstantia-Maria Chavele
1UCL Centre for Nephrology, Royal Free Hospital, London, UK. r.pepper@ucl.ac.uk
Insights
Serum calprotectin shows promise as a biomarker for antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). Elevated levels indicate active disease and potential relapse, even during remission, suggesting ongoing subclinical inflammation.
Area of Science:
- Immunology
- Nephrology
- Rheumatology
Background:
- Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) frequently causes glomerulonephritis.
- Neutrophils and monocytes play key roles in AAV pathogenesis.
- Calprotectin (S100A8/S100A9) is a neutrophil/monocyte-derived Toll-like receptor-4 ligand elevated in inflammation.
Purpose of the Study:
- To investigate calprotectin as a potential biomarker in AAV.
- To correlate calprotectin expression and levels with disease activity and renal pathology in AAV patients.
Main Methods:
- Immunohistochemistry of renal biopsies to assess calprotectin expression in glomerular lesions.
- Enzyme-linked immunosorbent assay (ELISA) to measure serum calprotectin levels.
- Flow cytometry to evaluate cell surface calprotectin expression on monocytes and neutrophils.
Main Results:
- Highest calprotectin expression in renal biopsies was observed in focal or crescentic glomerular lesions.
- Serum calprotectin levels were elevated in active AAV and decreased, but not normalized, during remission.
- Calprotectin levels increased with treatment withdrawal and were higher in patients who relapsed.
Conclusions:
- Serum calprotectin is a potential disease biomarker for AAV.
- Elevated calprotectin suggests subclinical inflammation and may predict relapse.
- Calprotectin may play a role in the pathogenesis of AAV.
Abstract:
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) commonly results in glomerulonephritis, in which neutrophils and monocytes have important roles. The heterodimer calprotectin (S100A8/S100A9, mrp8/14) is a Toll-like receptor-4 ligand found in neutrophils and monocytes and is elevated in inflammatory conditions. By immunohistochemistry of renal biopsies, patients with focal or crescentic glomerular lesions were found to have the highest expression of calprotectin and those with sclerotic the least. Serum levels of calprotectin as measured by ELISA were elevated in patients with active AAV and the levels decreased but did not normalize during remission, suggesting subclinical inflammation. Calprotectin levels in patients with limited systemic disease increased following treatment withdrawal and were significantly elevated in patients who relapsed compared with those who did not. As assessed by flow cytometry, patients with AAV had higher monocyte and neutrophil cell surface calprotectin expression than healthy controls, but this was not associated with augmented mRNA expression in CD14(+) monocytes or CD16(+) neutrophils. Thus, serum calprotectin is a potential disease biomarker in patients with AAV, and may have a role in disease pathogenesis.
