Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands with a heterogeneous constellation of extra glandular manifestations. SS may occur as the primary disease, or secondary to another connective tissue disease such as rheumatoid arthritis or systemic lupus erythematosus. The molecular events that lead to SS are poorly understood but thought to involve multiple components of immune dysregulation. Our overall goal is to define important biological pathways that are dysregulated in SS patients using microarray technologies to examine genomic-scale gene expression profiles. We have recently established that differential gene expression patterns can be identified using peripheral blood mononuclear cells and initial analyses to date suggest that dysregulation of interferon-inducible genes may be important in SS. Here, we propose to define gene expression signatures in a large cohort of weft characterized SS patients, evaluate potential correlations between gene expression signatures and various phenotypic components of disease, and examine the durability and relationship with disease manifestations of the gene expression signatures over time. We will also collect essential biological samples that will allow a variety of confirmatory studies to be conducted using complementary methods. Characterization of gene expression profiles in SS has a high likelihood of conferring novel and important insights in the pathophysiologic mechanisms of this disease, and providing an important source of potential targets for development of novel diagnostic and therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR050782-03
Application #
6945418
Study Section
Special Emphasis Panel (ZAR1-RJB-E (O1))
Program Officer
Serrate-Sztein, Susana
Project Start
2003-09-26
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$347,287
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Zhao, Jian; Ma, Jianyang; Deng, Yun et al. (2017) A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases. Nat Genet 49:433-437
Leehan, Kerry M; Pezant, Nathan P; Rasmussen, Astrid et al. (2017) Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren's syndrome. Autoimmunity 50:451-457
Rasmussen, Astrid; Radfar, Lida; Lewis, David et al. (2016) Previous diagnosis of Sjögren's Syndrome as rheumatoid arthritis or systemic lupus erythematosus. Rheumatology (Oxford) 55:1195-201
Rasmussen, Astrid; Ice, John A; Li, He et al. (2014) Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort. Ann Rheum Dis 73:31-8
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Lessard, Christopher J; Ice, John A; Adrianto, Indra et al. (2012) The genomics of autoimmune disease in the era of genome-wide association studies and beyond. Autoimmun Rev 11:267-75
Ice, John A; Li, He; Adrianto, Indra et al. (2012) Genetics of Sjögren's syndrome in the genome-wide association era. J Autoimmun 39:57-63
Segal, B M; Pogatchnik, B; Holker, E et al. (2012) Primary Sjogren's syndrome: cognitive symptoms, mood, and cognitive performance. Acta Neurol Scand 125:272-8

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