Immunoproteasome subunit LMP2 expression is deregulated in Sjögren'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\textgreeka and
PA28\textgreekb and of constitutive proteasome and
interferon-\textgreekg-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 (\textgreekb1i), LMP7 (\textgreekb5i),
MECL1 (\textgreekb2i), and PA28\textgreeka 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 Sjögren's syndrome. At the transcript level,
the interferon-\textgreekg-responsive subunits LMP2
(\textgreekb1i), MECL1 (\textgreekb2i), and the proteasome
activator subunit PA28\textgreeka were markedly up regulated. In
contrast, LMP2 (\textgreekb1i) deficiency was evident at the
protein level, indicating deregulation of proteasome expression in
Sjögren'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 (\textgreekb1i) in
the pathogenesis of primary Sjögren's syndrome.