title: Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis.
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.
authors: UCL Centre for Nephrology, Royal Free Hospital, London, UK. r.pepper@ucl.ac.uk
authors: Ruth J
authors: RJ
authors: Pepper
authors: Sally
authors: S
authors: Hamour
authors: Konstantia-Maria
authors: KM
authors: Chavele
authors: Sarah K
authors: SK
authors: Todd
authors: Niels
authors: N
authors: Rasmussen
authors: Shaun
authors: S
authors: Flint
authors: Paul A
authors: PA
authors: Lyons
authors: Kenneth G C
authors: KG
authors: Smith
authors: Charles D
authors: CD
authors: Pusey
authors: H Terence
authors: HT
authors: Cook
authors: Alan D
authors: AD
authors: Salama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D040501:Calgranulin A / Q000097:blood*; D040502:Calgranulin B / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood*; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D055503:Protein Multimerization; D012074:Remission Induction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D040501:Calgranulin A; D040502:Calgranulin B; D018836:Inflammation Mediators