TY - JOUR
T1 - Possible involvement of EBV-mediated α-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome
AU - Inoue, H.
AU - Tsubota, K.
AU - Ono, M.
AU - Kizu, Y.
AU - Mizuno, F.
AU - Takada, K.
AU - Yamada, K.
AU - Yanagi, K.
AU - Hayashi, Y.
AU - Saito, I.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2001/5/1
Y1 - 2001/5/1
N2 - A cleavage product of α-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of α-fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen α-fodrin. ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals. ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry. Furthermore, a significant link between production of Abs against 120-kDa α-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals. EBV-activated lymphoid cells showed specific α-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of α-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of α-fodrin proteolysis in the development of SS.
AB - A cleavage product of α-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of α-fodrin cleavage remain unclear. Since EBV has been implicated in the pathogenesis of SS, we determined whether EBV activation could induce the SS-specific 120-kDa autoantigen α-fodrin. ZEBRA mRNA expression, a marker for activation of the lytic cycle of EBV, was found in the salivary gland tissues from SS patients, but not in those from control individuals. ZEBRA-expressing lymphoid cells were also found in the SS glands in double-stained immunohistochemistry. Furthermore, a significant link between production of Abs against 120-kDa α-fodrin and reactivated EBV Ag was found in sera from patients with SS, but not in those from control individuals. EBV-activated lymphoid cells showed specific α-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of α-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of α-fodrin proteolysis in the development of SS.
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U2 - 10.4049/jimmunol.166.9.5801
DO - 10.4049/jimmunol.166.9.5801
M3 - Article
C2 - 11313424
AN - SCOPUS:0035340982
VL - 166
SP - 5801
EP - 5809
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -