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 PA28alpha and PA28beta 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 (beta1i), LMP7 (beta5i), MECL1 (beta2i), and PA28alpha 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-gamma-responsive subunits LMP2 (beta1i), MECL1 (beta2i), and the proteasome activator subunit PA28alpha were markedly up regulated. In contrast, LMP2 (beta1i) 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 (beta1i) in the pathogenesis of primary Sjögren's syndrome.
Krause
S
S
Laboratory of Molecular Myology, Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians University, Marchioninistrasse 17, 81377 Munich, Germany. sabine.krause@med.uni-muenchen.de
Kuckelkorn
U
U
Dörner
T
T
Burmester
G-R
GR
Feist
E
E
Kloetzel
P-M
PM
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000276:immunology*; D018709:Statistics, Nonparametric
D015415:Biomarkers; D009124:Muscle Proteins; C085047:PSME1 protein, human; D012333:RNA, Messenger; C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex