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Expression Of The Key Factors Of CGAS/STING Signaling Pathway In SLE And Correlation Analysis Between Type â…  Interferons And Indicators Of Disease Activity

Posted on:2015-01-26Degree:DoctorType:Dissertation
Country:ChinaCandidate:J J WuFull Text:PDF
GTID:1224330431497876Subject:Clinical Medicine
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Objective:To investigate expression of the key factors of cGAS/STING signaling pathway in peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients. To study expression of type I interferons (IFNs) of SLE patients and analysis correlation between type I interferons and indicators of disease activity.Methods:①Patients were divided into SLE high activity group (SLEDAI score≥10) and SLE low activity group (SLEDAI score<10) according to the SLEDAI score.②mRNA levels of the key factors of cGAS/STING signaling pathway, including cGAS, STING, TBK1, IRF3and type I IFNs in PBMC of SLE high activity group patients, SLE low activity group patients and normal controls were detected by Realtime PCR method.③Expression of IRF3protein in PBMC of SLE high activity group patients, SLE low activity group patients and normal controls were detected by Western Blot method.④Protein levels of IFN a and IFN (3in serum of SLE high activity group patients, SLE low activity group patients and normal controls were detected by ELISA method. And analysis correlation between type I IFNs and indicators of disease activity, including SELDAI score, autoimmune antibodies, and several clinical symptoms.Results:①cGAS, TBK1, STING, IFNβ mRNA levels in PBMC are not significantly different among SLE high activity group, SLE low activity group and normal controls. IRF3mRNA level in PBMC of SLE low activity group is significantly decreased compared with normal controls, IFNa mRNA level in PBMC of SLE high activity group patients is significantly decreased compared with normal controls.②Western Blot results suggests that there is no significant difference in expression of IRF3protein among three groups.③Serum IFNa level of SLE high activity group and low activity group patients significantly increased, compared with normal controls, and serum IFNa level of SLE high activity group is about2times of the SLE low activity group and normal control group. Serum levels of IFNβ have no significant difference between SLE high activity group and low activity group. Serum IFNβ of SLE high activity group and low activity group are increased about3-4times compared with normal controls.④Serum IFNa of SLE patients is positively correlated with SLEDAI score and negatively correlated with the duration of SLE, and may also correlated with anti-dsDNA antibody, antinucleosome antibody(ANuA), complement C4, lupus nephritis. Serum IFN(3of SLE patients is positively correlated with titer of antinuclear antibody (ANA).Conclusion:①The key factor of cGAS/STING signaling pathway, cGAS, STING and TBK1, exactly expressed in PBMC of SLE patients.②Serum expression levels of Type I interferons are increased in SLE groups and corelated with some disease activity indicators, including SLEDAI score, several autoantibodies and symptoms.
Keywords/Search Tags:Systemic lupus erythematosus, cGAS, STING, CytosolicDNA signaling pathway, type â…  interferons
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