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Persistent activation of the tumor necrosis factor system in a subgroup of
patients with common variable immunodeficiency--possible immunologic and
clinical consequences
P Aukrust, E Lien, AK Kristoffersen, F Muller, CJ Haug, T Espevik and SS Froland
Medical Department A, National Hospital, University of Oslo, Norway.
In patients with common variable immunodeficiency (CVI), we have previously
defined a subgroup of patients (CVIHyper) characterized by decreased
numbers of CD4+ lymphocytes in peripheral blood, splenomegaly, and
persistent immune activation in vivo, particularly of
monocytes/macrophages. To further characterize this hyperactivity,
parameters of activation of the tumor necrosis factor (TNF) system (TNF
alpha and soluble TNF receptors [sTNFRs]) were measured in 24 patients with
CVI and 20 healthy controls. Patients with CVI had significantly higher
serum levels of TNF alpha and both types of sTNFRs, with the highest levels
in the CVIHyper subgroup. In vitro, peripheral blood mononuclear cells
(PBMC) and purified monocytes from CVIHyper patients spontaneously released
significantly higher levels, and, after lipopolysaccharide (LPS)
stimulation, significantly lower levels of TNF alpha and soluble p75-TNFR
than cells from both other CVI patients and healthy controls. CVIHyper
patients also had significantly higher TNF alpha:sTNFRs ratios in both
serum and in unstimulated PMBC supernatants. The present study demonstrates
persistent in vivo activation of the TNF system in CVI, particularly in the
CVIHyper subgroup. This activation may contribute to the pathogenesis of
both clinical and immunologic manifestations in CVI.
Volume 87,
Issue 2,
pp. 674-681,
01/15/1996
Copyright © 1996 by The American Society of Hematology
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