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

Hjelmervik TO, Petersen K, Jonassen I, Jonsson R, Bolstad AI

Faculty of Dentistry, University of Bergen, Broegelmann Research Laboratory, University of Bergen, and Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. trond.hjelmervik@gades.uib.no

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 essential in saliva production and secretion, and the apoptosis regulator Bcl-2-like 2 were down-regulated in primary SS patients. CONCLUSION: We have identified distinct gene expression profiles in MSGs from patients with primary SS that provide new knowledge about groups of genes that are up-regulated or down-regulated during disease, constituting an excellent platform for forthcoming functional studies.

Published 11 May 2005 in Arthritis Rheum, 52(5): 1534-44.
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