Expression of proteasomal immunosubunit beta1i is dysregulated in inflammatory infiltrates of minor salivary glands in Sjogren's syndrome

• Published in: Journal of rheumatology 2009-12, Vol.36 (12), p.2694-2703
• Main Authors: Morawietz, Lars, Martinez-Gamboa, Lorena, Scheffler, Sonja, Hausdorf, Gert, Dankof, Anja, Kuckelkorn, Ulrike, Doerner, Thomas, Egerer, Karl, Burmester, Gerd-R, Faustman, Denise L, Feist, Eugen
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Animals; B-Lymphocyte Subsets - immunology; B-Lymphocytes - immunology; Biopsy; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Female; Humans; Lip - cytology; Lip - pathology; Male; Middle Aged; Molecular Sequence Data; Protein Subunits - genetics; Protein Subunits - immunology; Salivary Glands, Minor - immunology; Salivary Glands, Minor - metabolism; Salivary Glands, Minor - pathology; Sjogren's Syndrome - immunology; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocytes - immunology; Young Adult
• ISSN: 0315-162X
• DOI: 10.3899/jrheum.081098

Minor salivary gland specimens were analyzed to investigate dysregulation of the proteasome system in patients with Sjögren's syndrome (SS) and patients with sicca syndrome. Labial biopsy specimens from 17 patients with SS and 11 patients with non-autoimmunesicca syndrome were analyzed by immunohistochemistry for expression of the inducible proteasomal subunits ss1i, ss2i, and ss5i. The infiltrating subsets of lymphocytes were characterized using immunofluorescence stainings against the cell-surface markers CD20 and CD27. Two-dimensional electrophoresis and immunoblotting were used for detection of the proteasomal subunits ss1 and ss1i in peripheral blood monocyte cells. Gene expression of the constitutive subunits ss1, ss2, and ss5 and the corresponding inducible subunits ss1i, ss2i, and ss5i was further investigated at the mRNA level in small lip biopsies using real-time polymerase chain reaction. The expression of ss1i in infiltrating and peripheral immune cells was altered in patients with SS compared to patients with non-autoimmune sicca syndrome and healthy controls. No significant differences were found in ss2i and ss5i expression between the same groups in small lip biopsies. Chisholm-Mason grade and ss1i expression were found to be inversely correlated (Spearman r = -0.461, p = 0.014). The phenotype and distribution of the lymphocytic infiltrate showed no differences between patients with primary and secondary SS regardless of ss1i expression. The proteasomal ss1i subunit is dysregulated in peripheral white blood cells and in inflammatory infiltrates of minor salivary glands in patients with SS.