EXTENDED REPORT

Immunoproteasome subunit LMP2 expression is deregulated in Sjögren’s syndrome but not in other autoimmune disorders

S Krause^1,2,4, U Kuckelkorn¹, T Dörner³, G-R Burmester², E Feist^2,*, P-M Kloetzel^1,*

¹ Institute of Biochemistry, Charité-University Medicine Berlin, Germany
² Department of Medicine, Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Germany
³ Institute of Transfusion Medicine, Charité-University Medicine Berlin, Germany
⁴ Laboratory of Molecular Myology, Friedrich-Baur Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany

Correspondence to:
Dr S Krause
Friedrich-Baur-Institute, Laboratory of Molecular Myology, Department of Neurology, Ludwig-Maximilians University, Marchioninistr 17, 81377 Munich, Germany; sabine.krause{at}med.uni-muenchen.de

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 and PA28ß and of constitutive proteasome and interferon--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 (ß1i), LMP7 (ß5i), MECL1 (ß2i), and PA28 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--responsive subunits LMP2 (ß1i), MECL1 (ß2i), and the proteasome activator subunit PA28 were markedly up regulated. In contrast, LMP2 (ß1i) 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 (ß1i) in the pathogenesis of primary Sjögren’s syndrome.

Abbreviations: HPRT, hypoxanthine phosphoribosyl transferase; IFN, interferon ; LMP, low molecular weight protein; MECL1, multicatalytic endopeptidase complex-like 1; MHC, major histocompatibility complex; NOD, non-obese diabetic; PM, polymyositis; RA, rheumatoid arthritis; PA, proteasome activator; pSS, primary Sjögren’s syndrome; RT-PCR, reverse transcriptase-polymerase chain reaction; SLE, systemic lupus erythematosus; SSc, systemic sclerosis

Keywords: proteasome; autoimmune disorders; Sjögren’s syndrome; real time quantitative RT-PCR; interferon

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