PT - JOURNAL ARTICLE AU - Lorena Martinez-Gamboa AU - Karsten Lesemann AU - Ulrike Kuckelkorn AU - Sonja Scheffler AU - Khetam Ghannam AU - Martin Hahne AU - Timo Gaber-Elsner AU - Karl Egerer AU - Lydia Naumann AU - Frank Buttgereit AU - Thomas Dörner AU - Peter M. Kloetzel AU - Gerd R. Burmester AU - Denise L. Faustman AU - Eugen Feist TI - Gene Expression of Catalytic Proteasome Subunits and Resistance Toward Proteasome Inhibition of B Lymphocytes from Patients with Primary Sjögren Syndrome AID - 10.3899/jrheum.120680 DP - 2013 May 01 TA - The Journal of Rheumatology PG - 663--673 VI - 40 IP - 5 4099 - http://www.jrheum.org/content/40/5/663.short 4100 - http://www.jrheum.org/content/40/5/663.full SO - J Rheumatol2013 May 01; 40 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.