Autoimmune reactivity against the 20S-proteasome includes immunosubunits LMP2 (beta1i), MECL1 (beta2i) and LMP7 (beta5i).
OBJECTIVE
Autoantibodies against the 20S-proteasome display a broad diversity with a remarkably low frequency of individual cross-reactivity against the different subunits of the proteasome. Although their pathogenic and diagnostic significance remains obscure, an involvement in the clearance of circulating proteasomes as well as an interaction with the activity of the proteolytic complex was assumed in previous studies.


METHODS
To investigate the anti-proteasome response in more detail and to disclose reactivities against former neglected subunits, two-dimensional electrophoresis followed by immunoblotting was used. As a novel antigen source, the immunosubunits LMP2 (beta1i) and LMP7 (beta5i) were expressed as recombinant proteins and employed in ELISA.


RESULTS
The subunits Iota (alpha1) and Zeta (alpha5) of the outer rings as well as the catalytic subunit Delta (beta1) and all three immunosubunits [MECL-1 (beta2i), LMP2 (beta1i) and LMP7 (beta5i)] of the inner rings of the proteasome were identified as autoantigens for the first time. Using a panel of anti-proteasome antibody-positive sera of patients with SLE, autoimmune myositis (PM/DM) and primary Sjögren's syndrome (pSS), an autoimmune response was documented against LMP2 (beta1i) and LMP7 (beta5i) in all three patient groups in ELISA.


CONCLUSIONS
The frequent autoimmune response against LMP2 (beta1i) and LMP7 (beta5i) might indicate a role of inflammatory processes in the primary induction of the anti-proteasomal immune reaction, while the diversity of the humoral response against the proteasome system supports the assumption of a specific antigen-driven process leading to these extended autoimmune reactivities.
Scheffler
S
S
Department of Medicine/Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Kuckelkorn
U
U
Egerer
K
K
Dörner
T
T
Reiter
K
K
Soza
A
A
Burmester
G-R
GR
Feist
E
E
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000276:immunology; D009220:Myositis / Q000276:immunology; D011446:Prospective Studies; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology; D018709:Statistics, Nonparametric
D001323:Autoantibodies; D009097:Multienzyme Complexes; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex