To review recent experimental evidence on the involvement of autoantigens and autoantibodies in the pathogenesis of organ-specific autoimmunity in Sjögren syndrome (SS).
Among candidate autoantigens in SS, we investigated the role of alpha-fodrin in the lacrimal gland using a mouse model and a lacrimal gland cell line established in p53 knockout mice. We also tried to identify a novel organ-specific autoantigen by screening the human salivary gland cell line (HSG) against sera from SS patients. The specificity and sensitivity of this autoantigen to SS patient sera, its cellular localization, and the gene encoding the protein were analyzed.
In addition to the previously identified 120-kd alpha-fodrin in the salivary gland, a shorter fragment was detected, indicating that there may be a distinct apoptosis-related protease that cleaves alpha-fodrin in the lacrimal gland. A novel salivary gland-specific autoantibody was detected in 50.9% of sera from SS patients. The antigen recognized by this antibody may be a 45-kd nucleus protein not recognized in its native form.
The precise roles of autoantigens in organ-specific autoimmunity are still unclear, although accumulated evidence suggests that they may be associated with disease progression. Further studies of alpha-fodrin and the 45-kd antigen may contribute to the understanding of the pathogenesis of SS and may provide a new strategy for organ-specific therapy, such as vaccination with analogue peptides.