IADR Abstract Archives
The Role of Circadian Clock Disruption in Sjögren’s Syndrome
Objectives: Disruption of the circadian clock has a significant effect on the performance of the immune system and may negatively impact the pathogenesis of metabolic syndromes, cancer and autoimmune diseases. Sjögren’s Syndrome (SS) is a disease characterized by lymphocytic infiltration and exocrine failure of salivary and lacrimal glands, resulting in the patients’ suffering of xerostomia, chronic fatigue, pain, and pathogenic production of inflammatory cytokines. The circadian clock may regulate the expression and activity of several genes and proteins that are involved in the progression of autoimmune diseases, such as SS. We hypothesize that disruption of the circadian clock contributes in SS pathogenesis. The aim of this this project is to characterize circadian clock gene expression in SS and its correlations, if any, with disease progression.
Methods: We examine biopsy material of SS patients (n=10) and controls. The data collection includes patient-reported outcomes (pain, fatigue, etc.) and medical records data (patient gender and age, involvement of any other joint or organ, serology, and pathology report). We analyzed RNA expression and protein levels of clock genes in human salivary glands from healthy controls and SS patients using qRT-PCR and Immunohistochemistry. Clinical correlations between clock genes expression and disease severity are being evaluted by statistics.
Results: Clock gene RNA expression levels are found dramatically down-regulated, approximately 30-250-fold, in SS compared to healthy salivary glands. Immunohistochemistry showed down-regulation of circadian clock proteins expression in SS biopsies. Cell numbers were similar between SS and control samples. Preliminary data also revealed significant clock protein down-regulation in the patients with more severe SS as documented by positive SSA and SSB antibodies.
Conclusions: Given the prevalence of sleep disorders, shift work and busy lifestyles today, it is important to elucidate how body clock disturbances affect health and disease. Correlations found between the level of clock genes and disease progression and symptom severity may be used as novel diagnostic and prognostic tools. Manipulation of clock genes expression may correct saliva flow in patients with SS.
Methods: We examine biopsy material of SS patients (n=10) and controls. The data collection includes patient-reported outcomes (pain, fatigue, etc.) and medical records data (patient gender and age, involvement of any other joint or organ, serology, and pathology report). We analyzed RNA expression and protein levels of clock genes in human salivary glands from healthy controls and SS patients using qRT-PCR and Immunohistochemistry. Clinical correlations between clock genes expression and disease severity are being evaluted by statistics.
Results: Clock gene RNA expression levels are found dramatically down-regulated, approximately 30-250-fold, in SS compared to healthy salivary glands. Immunohistochemistry showed down-regulation of circadian clock proteins expression in SS biopsies. Cell numbers were similar between SS and control samples. Preliminary data also revealed significant clock protein down-regulation in the patients with more severe SS as documented by positive SSA and SSB antibodies.
Conclusions: Given the prevalence of sleep disorders, shift work and busy lifestyles today, it is important to elucidate how body clock disturbances affect health and disease. Correlations found between the level of clock genes and disease progression and symptom severity may be used as novel diagnostic and prognostic tools. Manipulation of clock genes expression may correct saliva flow in patients with SS.