Department of Rheumatology and Clinical Immunology, Institute of Pathology, and Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
J Rheumatol. 2009 Dec;36(12):2694-703. doi: 10.3899/jrheum.081098. Epub 2009 Oct 15.
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.
分析小唾液腺标本,以研究干燥综合征(SS)患者和干燥综合征患者的蛋白酶体系统失调。
通过免疫组织化学分析 17 例 SS 患者和 11 例非自身免疫性干燥综合征患者的唇活检标本,检测诱导型蛋白酶体亚基 ss1i、ss2i 和 ss5i 的表达。使用针对细胞表面标志物 CD20 和 CD27 的免疫荧光染色来鉴定淋巴细胞浸润亚群。使用二维电泳和免疫印迹法检测外周血单核细胞中蛋白酶体亚基 ss1 和 ss1i 的表达。使用实时聚合酶链反应进一步研究小唇活检中小唾液腺中组成型亚基 ss1、ss2 和 ss5 以及相应的诱导型亚基 ss1i、ss2i 和 ss5i 的基因表达。
与非自身免疫性干燥综合征患者和健康对照组相比,SS 患者浸润和外周免疫细胞中的 ss1i 表达发生改变。在小唇活检中,相同组之间的 ss2i 和 ss5i 表达没有发现显著差异。Chisholm-Mason 分级和 ss1i 表达呈负相关(Spearman r = -0.461,p = 0.014)。无论 ss1i 表达如何,原发性和继发性 SS 患者的淋巴细胞浸润的表型和分布均无差异。
在 SS 患者的外周白细胞和小唾液腺炎症浸润中,蛋白酶体 ss1i 亚基失调。