Autoimmune reactivity against the 20S-proteasome includes immunosubunits LMP2 (beta 1i), MECL1 (beta 2i) and LMP7 (beta 5i)

Abstract

Objectives. 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 (beta 1i) and LMP7 (beta 5i) were expressed as recombinant proteins and employed in ELISA.

Results. The subunits Iota (alpha 1) and Zeta (alpha 5) of the outer rings as well as the catalytic subunit Delta (beta 1) and all three immunosubunits [MECL-1 (beta 2i), LMP2 (beta 1i) and LMP7 (beta 5i)] 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 Sjgrens syndrome (pSS), an autoimmune response was documented against LMP2 (beta 1i) and LMP7 (beta 5i) in all three patient groups in ELISA.

Conclusions. The frequent autoimmune response against LMP2 (beta 1i) and LMP7 (beta 5i) 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.