Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis

Diez-Ruiz A, et al. Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria
(Eur J Haematol 1995; 54: 1-8)

Soluble tumour necrosis factor receptors (sTNF-Rs) play a role as modulators of the biological function of tumour necrosis factor-alpha (TNF-alpha) in an agonist/antagonist pattern. In various pathologic states the production and release of sTNF-Rs may mediate host response and determine the course and outcome of disease by interacting with TNF-alpha and competing with cell surface receptors. The determination of sTNF-Rs in body fluids such as plasma or serum is a new tool to gain information about immune processes and provides valuable insight into a variety of pathological conditions. Regarding its immediate clinical use, sTNF-Rs levels show high accuracy in the follow-up and prognosis of various diseases. In HIV infection and sepsis, sTNF-Rs concentrations strongly correlate with the clinical stage and the progression of disease and can be of predictive value. Determination of sTNF-Rs also gives useful information for monitoring cancer and autoimmune diseases. The information provided is often even superior to that obtained with classical disease markers, probably due to the direct involvement of the "TNF system" in the pathogenetic mechanisms in these patients. The available data imply that the measurement of sTNF-Rs, especially of the sTNF-R 75kD type, is a useful adjunct for quantification of the Th1-type immune response, similar to other immune activation markers such as neopterin and beta 2-microglobulin. Endogenous sTNF-Rs concentrations appear to reflect the activation state of the TNF-alpha/TNF receptor system.

Increased serum concentrations of soluble tumor necrosis factor receptors in HIV-infected individuals are associated with immune activation.

Zangerle R, et al. Department of Dermatology and Venereology, University of Innsbruck, Innsbruck, Austria
(J Acquir Immune Defic Syndr 1994; 7: 79-85)

Serum concentrations of soluble tumor necrosis factor receptors (sTNF-Rs) were measured in 61 human immunodeficiency virus (HIV)-infected individuals. Thirty-five percent of these had increased serum concentrations of sTNF-R type I (p55) (sTNF-R55) and 82% had increased concentrations of sTNF-R type II (p75) (sTNF-R75). The extent of the increase of sTNF-R75 was greater in more advanced HIV infection (p = 0.046) as it was measured by dividing the 61 individuals into two groups according to the median of the CD4+ T-cell count. However, the increase in concentrations of sTNF-R55 in the group with a CD4+ T-cell count below the median was only moderate and did not reach statistical significance. A strong correlation was found between sTNF-R75 and the soluble immune activation markers beta 2-microglobulin (rs = 0.74, p < 0.0001) and urinary neopterin (rs = 0.67, p < 0.0001), and a less strong correlation was found with interferon-gamma (rs = 0.51, p = 0.0001). The correlations observed for sTNF-R55 were also significant but were always weaker than that of sTNF-R75. A weak inverse correlation was found between the number of CD4+ T cells and sTNF-R75 (rs = -0.33, p = 0.012), but no such correlation was observed with sTNF-R55. Our findings suggest that increased concentrations of serum sTNF-Rs in HIV infection are linked to immune activation, in which synergistic actions of interferon-gamma and the TNF-alpha system are likely to play an important role.

Serum soluble tumour necrosis factor receptor 55 is increased in patients with haematological neoplasias and is associated with immune activation and weight loss

Denz H, et al. Clinic of Internal Medicine, Kantonsspital Liestal, Switzerland
(Eur J Cancer 1993; 29A: 2232-5)

Enhanced concentrations of soluble forms of the receptor for tumour necrosis factor (TNF)-alpha have been detected in the serum of cancer patients. We determined serum concentrations of soluble TNF receptor p55 (sTNF-R55) in patients with haematological neoplasias, 50 patients suffering from non-Hodgkin's lymphoma (n = 35), Hodgkin's disease (n = 10) and multiple myeloma (n = 5). Compared with healthy controls and with patients with potential thyroid disease, significantly elevated concentrations of sTNF-R55 were found (mean +/- standard error: 2.68 +/- 0.22 vs. 1.23 +/- 0.21 ng/ml, P < 0.0001 and 2.18 +/- 0.32 ng/ml, P = 0.03). Likewise, neopterin concentrations were raised (19.6 +/- 3.66 vs. 5.3 +/- 0.25 nmol/l in controls, P < 0.0001). We found a significant correlation between sTNF-R55 and neopterin concentrations (Rs = 0.544, P < 0.001). Patients with weight loss showed higher sTNF-R55 concentrations than patients with stable weight. Our results confirm the relevance of sTNF-R55 concentrations in serum of patients with cancer.