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Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Pepper, Ruth J 
Hamour, Sally 
Chavele, Konstantia-Maria 
Todd, Sarah K 
Rasmussen, Niels 

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.

Description

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Analysis of Variance, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Biomarkers, Biopsy, Calgranulin A, Calgranulin B, Case-Control Studies, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Glomerulonephritis, Humans, Immunohistochemistry, Inflammation Mediators, Kidney, Leukocytes, Male, Middle Aged, Neutrophils, Predictive Value of Tests, Prognosis, Protein Multimerization, Remission Induction, Young Adult

Journal Title

Kidney Int

Conference Name

Journal ISSN

0085-2538
1523-1755

Volume Title

83

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (083650/Z/07/Z)
Medical Research Council (G0400929)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (079895/Z/06/B)