RT Journal Article SR Electronic T1 Gene Expression of Catalytic Proteasome Subunits and Resistance Toward Proteasome Inhibition of B Lymphocytes from Patients with Primary Sjögren Syndrome JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.120680 DO 10.3899/jrheum.120680 A1 Lorena Martinez-Gamboa A1 Karsten Lesemann A1 Ulrike Kuckelkorn A1 Sonja Scheffler A1 Khetam Ghannam A1 Martin Hahne A1 Timo Gaber-Elsner A1 Karl Egerer A1 Lydia Naumann A1 Frank Buttgereit A1 Thomas Dörner A1 Peter M. Kloetzel A1 Gerd R. Burmester A1 Denise L. Faustman A1 Eugen Feist YR 2013 UL http://www.jrheum.org/content/early/2013/03/13/jrheum.120680.abstract AB Objective Dysregulation of proteasome subunit β1i expression has been shown in total blood mononuclear cells (PBMC) from patients with primary Sjögren syndrome (pSS), a B cell-driven systemic autoimmune disorder. Methods Proteasome activation was investigated in sorted blood cells from patients with pSS and controls by measuring transcript levels of constitutive (β1/β2/β5) and corresponding immunoproteasome catalytic subunits (β1i/β2i/β5i) using real-time PCR. At protein level, β1i protein expression was analyzed by immunoblotting. Functional effects of proteasome inhibition on proteolytic activity and induction of apoptosis were also evaluated in cellular subsets. Results The proteasome was found to be activated in pSS, with upregulation of gene expression of catalytic proteasome subunits. Western blot analysis revealed decreased β1i protein expression in pSS B lymphocytes, with decreased protein despite increased messenger RNA (mRNA) levels. After proteasome inhibition in vitro, proteolytic activity was less reduced and resistance to apoptosis was increased in B lymphocytes compared to other cells. Conclusion In pSS, catalytic subunits of the proteasome are upregulated at the mRNA level, while dysregulation of subunit β1i is attributed to B lymphocytes. B cell resistance after proteasome inhibition differs from the classical concept of increased susceptibility toward inhibition in activated cells, supporting the novel notion that susceptibility depends on cellular intrinsic factors and on proteasome activation.