The proteasome, the main enzymatic complex for degradation of intracellular proteins, is emerging as a potential biomarker for chronic inflammatory diseases. Its activity is impaired by cigarette smoke and in lung tissue of COPD patients. Population-based studies focusing on proteasome profiling from peripheral blood mononuclear cells (PBMC) for stratifying COPD severity and progression are missing.

We profiled proteasome activity and expression of COSYCONET patients and validate proteasome function as a biomarker for COPD severity and endotypes.

PBMCs were obtained from 378 COSYCONET patients. Activity-based probes were used to quantify total proteasome activity and the six distinct standard (?1, ?2, ?5) and immunoproteasome (LMP2, MECL1, LMP7) activities. Relative RNA expression of multiple proteasome subunits (PSMA3, PSMB[5-10], PSMC3, PSMD11, PSME1) was determined by RTqPCR. Linear regression was used to analyze the association of COPD stages and BODE index with proteasome function.

The activity ratio of the catalytic subunits LMP7 and ?5 significantly decreased with increasing BODE index among females (%difference -48.5% (95%CI -70.4; -10.1) for index 1-2 and -46.5% (-70.0; -4.8) for index ?3 compared to index 0) but not among males. These changes in activity levels were not accompanied by significantly altered expression levels of the subunits PSMB5 (encoding ?5) and PSMB8 (encoding LMP7). 

Non-transcriptional mechanisms are associated with the downregulation of proteasome activity in COPD. Further proteasome function analyses of healthy subjects of the KORA cohort are in preparation to provide insight in proteasome activity and expression patterns among COPD patients compared to lung healthy controls.