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

Abstract

A cleavage product of alpha-fodrin may be an important organ-specific autoantigen in the pathogenesis of Sjogren's syndrome (SS), but the mechanisms of alpha-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 alpha-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 alpha-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 alpha-fodrin cleavage to the expected 120-kDa fragments in vitro. Pretreatment with caspase inhibitors inhibited cleavage of alpha-fodrin. Thus, an increase in apoptotic protease activities induced by EBV reactivation may be involved in the progression of alpha-fodrin proteolysis in the development of SS.

• Authors: H Inoue, K Tsubota, M Ono, Y Kizu, F Mizuno, K Takada, K Yamada, K Yanagi, Y Hayashi, I Saito
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 9 Pg. 5801-9 (May 01 2001) ISSN: 0022-1767 [Print] United States
• PMID: 11313424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Autoantigens
• BZLF1 protein, Herpesvirus 4, Human
• Carrier Proteins
• Cysteine Proteinase Inhibitors
• DNA-Binding Proteins
• Leupeptins
• Microfilament Proteins
• Pepstatins
• Trans-Activators
• Viral Proteins
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• fodrin
• Streptomyces pepsin inhibitor
• Aprotinin
• Caspases
• Leucine
• ubenimex
• leupeptin
• E 64
• pepstatin

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Apoptosis (immunology)
• Aprotinin (pharmacology)
• Autoantigens (biosynthesis, immunology, metabolism)
• Carrier Proteins (antagonists & inhibitors, biosynthesis, immunology, metabolism)
• Caspases (metabolism)
• Cysteine Proteinase Inhibitors (pharmacology)
• DNA-Binding Proteins (biosynthesis)
• Herpesvirus 4, Human (immunology)
• Humans
• Hydrolysis
• Leucine (analogs & derivatives, pharmacology)
• Leupeptins (pharmacology)
• Microfilament Proteins (antagonists & inhibitors, biosynthesis, immunology, metabolism)
• Molecular Weight
• Organ Specificity (immunology)
• Pepstatins (pharmacology)
• Sjogren's Syndrome (enzymology, immunology, virology)
• Trans-Activators (biosynthesis)
• Tumor Cells, Cultured (cytology, enzymology, metabolism)
• Viral Proteins (biosynthesis)
• Virus Activation (immunology)