Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects

作者：Trond Ove R. Hjelmervik, Kjell Petersen, Inge Jonassen, Roland Jonsson, Anne Isine Bolstad · 发表于：Arthritis & Rheumatism · 年份：2005 · DOI：10.1002/art.21006 · 被引用次数：361 · 研究领域：Salivary Gland Disorders and Functions、GDF15 and Related Biomarkers、Diabetes and associated disorders

OBJECTIVE: To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). METHODS: A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. RESULTS: We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in </=10% of the controls. Lymphotoxin beta, as well as a number of major histocompatibility complex genes, cytokines, and lymphocyte activation factors, manifested its role in the pathogenesis of SS. Numerous type I interferon genes related to virus infection were found among the top 200 genes, with increased expression in primary SS. Interestingly, the expression of carbonic anhydrase II, which is es...