Immunoproteasome subunit LMP2 expression is deregulated in Sjogren's syndrome but not in other autoimmune disorders

Background: The proteasome system has a pivotal role in the control of the immune response, which suggests that it might be involved in the pathogenesis of autoimmune disorders. Objective: To investigate the expression profile of selected proteasomal genes in human peripheral blood mononuclear cells in patients with a variety of autoimmune diseases compared with healthy subjects. Methods: Real time quantitative RT-PCR was used to analyse the mRNA expression pattern of the proteasome activator subunits PA28 alpha and PA28 beta and of constitutive proteasome and interferon-gamma-inducible immunoproteasome subunits in peripheral blood mononuclear cells. Simultaneously, protein expression of selected proteasome subunits was quantified by immunoblotting. Results: Under systemic inflammatory conditions the proteasome subunits LMP2 ( beta 1i), LMP7 ( beta 5i), MECL1 ( beta 2i), and PA28 alpha were expressed abundantly at the protein level in the vast majority of systemic autoimmune disorders. However, simultaneous mRNA and protein quantification showed a characteristic proteasome expression signature in primary Sjogren's syndrome. At the transcript level, the interferon-gamma-responsive subunits LMP2 ( beta 1i), MECL1 ( beta 2i), and the proteasome activator subunit PA28 alpha were markedly up regulated. In contrast, LMP2 ( beta 1i) deficiency was evident at the protein level, indicating deregulation of proteasome expression in Sjogren's syndrome. Conclusions: These data provide evidence for a regulatory defect in the proteasome system in human autoimmune disorders, pointing to a unique role for LMP2 ( b1i) in the pathogenesis of primary Sjogren's syndrome.