Leukocyte and serum S100A8/S100A9 expression reflects disease activity in ANCA-associated vasculitis and glomerulonephritis
Author(s)
Type
Journal Article
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 CD14þ monocytes or
CD16þ neutrophils. Thus, serum calprotectin is a potential
disease biomarker in patients with AAV, and may have a role
in disease pathogenesis.
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 CD14þ monocytes or
CD16þ neutrophils. Thus, serum calprotectin is a potential
disease biomarker in patients with AAV, and may have a role
in disease pathogenesis.
Date Issued
2013-02-20
Date Acceptance
2012-11-16
Citation
Kidney International, 2013, 83 (6), pp.1150-1158
ISSN
1523-1755
Publisher
Nature Publishing Group
Start Page
1150
End Page
1158
Journal / Book Title
Kidney International
Volume
83
Issue
6
Copyright Statement
© 2013 International Society of Nephrology. This work is licensed under the Creative
Commons Attribution-NonCommercial-No
Derivative Works 3.0 Unported License. To view a copy of
this license, visit http://creativecommons.org/licenses/by-ncnd/3.0/
Commons Attribution-NonCommercial-No
Derivative Works 3.0 Unported License. To view a copy of
this license, visit http://creativecommons.org/licenses/by-ncnd/3.0/
Subjects
Science & Technology
Life Sciences & Biomedicine
Urology & Nephrology
UROLOGY & NEPHROLOGY
ANCA
glomerulonephritis
immunology
macrophages
pathology
vasculitis
ANTIBODY-ASSOCIATED VASCULITIS
JUVENILE IDIOPATHIC ARTHRITIS
SYSTEMIC-LUPUS-ERYTHEMATOSUS
ENDOTHELIAL-CELLS
RECEPTOR 4
RHEUMATOID-ARTHRITIS
PROTEINS 8
REMISSION
MACROPHAGES
MRP14
Publication Status
Published