International Immunology, Vol. 16, No. 1, pp. 169-177,
January 2004
© 2004 Japanese Society for Immunology
Identification and characterization of a novel spliced variant that encodes human soluble tumor necrosis factor receptor 2
1 Immunology Unit, Department of Cellular Biology and Pathology, Medical School, University of Barcelona, Institut d‘Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain 2 Diabetes Unit, Endocrinology and Nutrition, University Hospital of Girona ‘Dr Josep Trueta’, 17007 Girona, Spain 3 Department of Physiology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain 4 Department of Rheumatology, Hospital Clinic, Barcelona, Institut d‘Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain
Correspondence to: P. Engel; E-mail: engel{at}medicina.ub.es
Transmitting editor: D. Wallach
Tumor necrosis factor (TNF)-
is a pleiotropic cytokine involved in a broad spectrum of inflammatory and immune responses including proliferation, differentiation and cell death induction in several cell types. The biological effects of TNF- are mediated via the cell-surface TNF receptors TNFR1 and TNFR2. Soluble forms of these two receptors, which contain the extracellular ectodomains, are proteolytically cleaved from the membrane. High levels of soluble (s) TNFR2 in serum have been documented in multiple inflammatory pathologies. We describe here a new differential spliced isoform of human TNFR2 missing exons 7 and 8, DS-TNFR2(
7,8). This novel isoform lacks the transmembrane and cytoplasmic domains. Expression studies with DS-TNFR2(7,8) cDNA transiently transfected COS cells showed that it encodes a sTNFR2 receptor of 
42 kDa. Soluble DS-TNFR2(7,8) blocked TNF--induced apoptosis, which suggests that it regulates TNF- function by antagonizing its biological activity. An ELISA was developed that quantifies sTNFR2 generated by alternative splicing. Our data show that sTNFR2 generated by alternative splicing can be found in sera of healthy individuals, at increased levels in patients with sepsis and at high concentrations in rheumatoid arthritis patients.
Keywords: inflammation, soluble cytokine receptor, tumor necrosis factor receptor
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