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Department of
Clinical Immunology, University Hospital Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands
Correspondence to: Dr A C Muller Kobold.
Accepted for publication 11 January 1999
OBJECTIVE
Wegener's
granulomatosis (WG) is an inflammatory disorder characterised by
granulomatous inflammation, vasculitis, and necrotising vasculitis and
is strongly associated with anti-neutrophil cytoplasmic antibodies
(ANCA). Activated monocytes/macrophages are present in renal biopsy
specimens and participate in granuloma formation by synthesising and
secreting a variety of chemoattractants, growth factors, and cytokines.
In view of these findings, in vivo monocyte activation was evaluated in
patients with WG and the findings related to parameters of clinical
disease activity.
METHODSMonocyte
activation was analysed by measuring plasma concentrations of soluble
products of monocyte activation, that is neopterin and interleukin 6 (IL6), by ELISA, and by quantitating the surface expression of
activation markers on circulating monocytes by flow cytometry.
RESULTSTwenty four
patients with active WG were included in this study. Ten of these
patients were also analysed at the time of remission. Twelve patients
with sepsis served as positive controls, and 10 healthy volunteers as
negative controls for monocyte activation. Patients with active disease
had increased monocyte activation compared with healthy controls as
shown by increased concentrations of neopterin (p <0.0001) and
increased surface expression of CD11b (p < 0.05) and CD64 (p < 0.05).
In those patients with increased concentrations of IL6 during active
disease plasma concentrations of IL6 decreased during follow up when
patients went into remission (p < 0.0001). In addition, neopterin
(r = 0.37, r = 0.44), IL6 (r = 0.37, r = 0.60) and CD63 expression
(r = 0.39, r = 0.45) correlated significantly with disease activity as measured by the
Birmingham Vasculitis Activity Score and C reactive protein values,
respectively. Compared with patients with sepsis, all markers of
monocyte activation in patients with vasculitis were lower.
CONCLUSIONIt is
concluded that disease activity in WG correlates with the extent of
activation of monocytes, compatible with their role in the
pathophysiology of this disease.
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