Increased levels of soluble Fas ligand in CSF of rapidly progressive HTLV-1-associated myelopathy/tropical spastic paraparesis patients.
The interaction of Fas ligand (FasL) with Fas-bearing cells induces apoptosis and contributes to the negative regulation of peripheral T-cell responses. Membrane-bound FasL is cleaved by a matrix metalloproteinase-like enzyme and converted to a soluble form (sFasL). Recent studies suggest that such sFasL can cause systemic tissue damage. Here we report that serum and CSF levels of soluble FasL (sFasL) are markedly higher in three active phase patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). All of these patients showed higher sFasL levels in CSF than in serum. Although the HTLV-1 proviral load of patients showed no correlation with serum or with CSF sFasL, CSF sFasL levels of 14 HAM/TSP patients correlated with the anti-HTLV-1 antibody titer and neopterin concentration in CSF. These results indicate that sFasL mediated mechanisms may contribute to the inflammatory process and subsequent spinal tissue damage seen in HAM/TSP patients.
Saito
M
M
Third Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan. m.saito@ic.ac.uk
Nakamura
N
N
Nagai
M
M
Shirakawa
K
K
Sato
H
H
Kawahigashi
N
N
Furukawa
Y
Y
Usuku
K
K
Nakagawa
M
M
Izumo
S
S
Osame
M
M
D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D053222:Fas Ligand Protein; D005260:Female; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000134:cerebrospinal fluid* / Q000276:immunology; D008875:Middle Aged; D019798:Neopterin / Q000276:immunology; D015493:Paraparesis, Tropical Spastic / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012995:Solubility; D019562:Viral Load
D000914:Antibodies, Viral; D000956:Antigens, Viral; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019798:Neopterin