Detection of the soluble form of the Fas molecule in patients with multiple sclerosis and human T-lymphotropic virus type I-associated myelopathy
Introduction
The Fas/Apo-1 molecule (designated as CD95) is an apoptosis-signaling receptor on the surface of a number of cell types. It belongs to the nerve growth factor–tumor necrosis factor–α-receptor family (Ito et al., 1991). Fas-mediated apoptosis seems to play an important role for the pathogenesis of autoimmune disease. Defects in the mouse Fas gene lead to autoimmune features in mice (Adachi et al., 1993). Levels of soluble Fas (sFas) were elevated in patients with systemic lupus erythematosus and rheumatoid arthritis, and mice injected with soluble Fas displayed autoimmune features (Cheng et al., 1994). Fas may also play an important role in viral infections such as influenza virus (Takizawa et al., 1993) and HTLV-1 (Debatin et al., 1990).
Though the pathogenesis of human multiple sclerosis (MS) is unknown, the autoimmune mechanism against neural antigen may be very important. Human T-lymphotropic virus type I (HTLV-I)-associated neurological disease mainly involving the spinal cord has been diagnosed as HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) (Osame et al., 1987). Though the causative virus for central nervous system (CNS) destruction is HTLV-I, the direct infection is not critical (Lehky et al., 1995), and apoptosis may play an important role for the pathogenesis (Debatin et al., 1990; Elovaara et al., 1993; Kira et al., 1992; Hara et al., 1994; Tabira et al., 1994). Taken together, there are possibilities that Fas is involved in the pathogenesis of both MS and HAM. Recently highly sensitive enzyme-linked immunosorbent assay for soluble Fas was developed (Seishima et al., 1996). Since the soluble form of the Fas molecule has not been studied in these diseases yet, we examined the levels of soluble Fas in the sera and CSF of patients with MS and HAM by using this ELISA system.
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Subjects and methods
The study population consisted of 51 patients with MS, 25 with HAM, 10 with other inflammatory neurological diseases, and 8 healthy volunteers.
Soluble Fas levels in serum of patients with multiple sclerosis and HAM
Standard curve was obtained as manufacturer's protocol.
MS patients in active stage (808.3±298.8 pg/ml) had significantly higher levels of serum sFas than MS patients in inactive stage (400.9±97.1 pg/ml; p<0.005), controls (412.0±125.4 pg/ml; p<0.005) and other neurological diseases (498.6±198.6; p<0.005) (Fig. 1(a)).
The levels of sFas in the sera of patients with HAM (1132.2±489.4 pg/ml) were significantly higher than other inflammatory neurological diseases and controls (p<0.005). There was no
Discussion
We have investigated serum and CSF levels of sFas in MS, an autoimmune demyelinating disease-associated inflammation, and HAM, which is characterized histologically by gliosis and mononuclear cell infiltrates around blood vessels. As far as we know, this is the first report that examined the soluble Fas antigen in sera and CSF of patients with MS and HAM. Apoptosis is a genetically encoded cell death program defined by characteristic morphologic and biochemical changes. A key molecule in the
Acknowledgements
The authors would like to thank Prof. S. Yonehara for his critical review of the manuscript and his helpful suggestions. This work was supported by grants (06670647, 07670707, 07457155) from the Ministry of Education and Culture and by a research grant for the neuroimmunological disease from Ministry of Health and Welfare, Japan. We would like to thank Dr. N. Hanyu, Dr. S. Nakagawa, Dr. K. Hohnoki for sample collection.
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