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1.  Peripheral blood gene expression profiling in Sjögren’s syndrome 
Genes and Immunity  2009;10(4):285-296.
Sjögren’s syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. Affected cases commonly present with oral and ocular dryness, thought to be the result of inflammatory cell-mediated gland dysfunction. To identify important molecular pathways involved in SS, we used high-density microarrays to define global gene expression profiles in peripheral blood. We first analyzed 21 SS cases and 23 controls and identified a prominent pattern of overexpressed genes that are inducible by interferons (IFNs). These results were confirmed by evaluation of a second independent dataset of 17 SS cases and 22 controls. Additional inflammatory and immune-related pathways with altered expression patterns in SS cases included B and T cell receptor, IGF-1, GM-CSF, PPARα/RXRα, and PI3/AKT signaling. Exploration of these data for relationships to clinical features of disease revealed that expression levels for most IFN-inducible genes were positively correlated with titers of anti-Ro/SSA (P<0.001) and anti-La/SSB (P<0.001) autoantibodies. Diagnostic and therapeutic approaches targeting IFN signaling pathway may prove most effective in the subset of SS cases who produce anti-Ro/SSA and anti-La/SSB autoantibodies. Our results strongly support innate and adaptive immune processes in the pathogenesis of SS and provide numerous candidate disease markers for further study.
doi:10.1038/gene.2009.20
PMCID: PMC3273959  PMID: 19404300
2.  Prevalence, Severity and Predictors of Fatigue in Primary Sjogren’s Syndrome 
Arthritis and rheumatism  2008;59(12):1780-1787.
OBJECTIVES
To investigate the relationship of fatigue severity to other clinical features in primary Sjogren’s syndrome (PSS) and to identify factors contributing to the physical and mental aspects of fatigue.
METHODS
We identified 94 subjects who met the American-European consensus criteria for the classification of PSS. Fatigue was assessed with a VAS, the Fatigue Severity Scale (FSS) and the Profile of Fatigue (ProF.) Associations with fatigue was compared using multivariate regression.
RESULTS
Abnormal fatigue defined as a FSS score of greater than or equal to 4 was present in 67% of the patients. Pain, helplessness and depression were the strongest predictors of both FSS and the somatic fatigue domain of the ProF (Prof-S), both with and without adjustment for physiologic and serologic characteristics. Depression was associated with higher levels of fatigue; however, the majority of patients with abnormal fatigue were not depressed. Anti-Ro/SSA positive patients were no more likely to report fatigue than seronegative patients. The regression models explained 62% of the variance in FSS and 78% of the variance in Prof-S. Mental fatigue was correlated with depression and helplessness, but the model predicted only 54% of the variance in mental fatigue (Prof-M.).
CONCLUSIONS
Psychosocial variables are determinants of fatigue, but only partly account for it. While fatigue is associated with depression, depression is not the primary cause of fatigue in PSS. Investigation of the pathophysiologic correlates of physical and mental aspects of fatigue is needed to guide the development of more effective interventions.
doi:10.1002/art.24311
PMCID: PMC3106978  PMID: 19035421

Results 1-2 (2)