Possible involvement of EBV-mediated α-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome

H. Inoue, K. Tsubota, M. Ono, Y. Kizu, F. Mizuno, K. Takada, K. Yamada, K. Yanagi, Y. Hayashi, I. Saito

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46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5801-5809
Number of pages9
JournalJournal of Immunology
Volume166
Issue number9
DOIs
Publication statusPublished - 2001 May 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Inoue, H., Tsubota, K., Ono, M., Kizu, Y., Mizuno, F., Takada, K., Yamada, K., Yanagi, K., Hayashi, Y., & Saito, I. (2001). Possible involvement of EBV-mediated α-fodrin cleavage for organ-specific autoantigen in Sjogren's syndrome. Journal of Immunology, 166(9), 5801-5809. https://doi.org/10.4049/jimmunol.166.9.5801