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1996-03-09
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Document 0513
DOCN M9650513
TI Persistent activation of the tumor necrosis factor system in a subgroup
of patients with common variable immunodeficiency--possible immunologic
and clinical consequences.
DT 9605
AU Aukrust P; Lien E; Kristoffersen AK; Muller F; Haug CJ; Espevik T;
Froland SS; Medical Department A, National Hospital, University of
Oslo,; Norway.
SO Blood. 1996 Jan 15;87(2):674-81. Unique Identifier : AIDSLINE
MED/96141088
AB 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.
DE Adult Aged Common Variable
Immunodeficiency/CLASSIFICATION/COMPLICATIONS/
IMMUNOLOGY/*PHYSIOPATHOLOGY Comparative Study CD4 Lymphocyte Count
Female Human Immunophenotyping Leukocytes, Mononuclear/DRUG
EFFECTS/SECRETION Lipopolysaccharides/PHARMACOLOGY Male Middle Age
Receptors, Tumor Necrosis Factor/ANALYSIS Splenomegaly/ETIOLOGY
Support, Non-U.S. Gov't Tumor Necrosis Factor/*PHYSIOLOGY JOURNAL
ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).