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

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