leupeptins and Sjogren-s-Syndrome

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.

Topics: Amino Acid Chloromethyl Ketones; Apoptosis; Aprotinin; Autoantigens; Carrier Proteins; Caspases; Cysteine Proteinase Inhibitors; DNA-Binding Proteins; Herpesvirus 4, Human; Humans; Hydrolysis; Leucine; Leupeptins; Microfilament Proteins; Molecular Weight; Organ Specificity; Pepstatins; Sjogren's Syndrome; Trans-Activators; Tumor Cells, Cultured; Viral Proteins; Virus Activation